Post-burn immunosuppression and immune cell dysfunction

Overview¶

Post-burn immunosuppression is the immune substrate of the infection and sepsis that kill most patients who survive the initial resuscitation. More than 30 years of investigation documented immunologic abnormalities after burn across serum immunoglobulins, the complement system, phagocyte and neutrophil function, and lymphocyte responses ^[1]. Extensively burned patients have increased susceptibility to infection and often die of multiple organ failure related to sepsis ^[1]. Infection is the leading cause of death in hospitalized burn patients without inhalation injury, accounting for between 50 and 75% of hospital deaths ^[3]. Sepsis is responsible for roughly 75% of late deaths after major thermal injury ^[4] and accounts for 47% of postburn mortality ^[5].

The modern frame is a continuous, time-dependent process rather than a staged entity. Severe burn drives an early hyperinflammatory phase superimposed on, and followed by, a prolonged anti-inflammatory immunoparalysis ^[10]. The concept now encompasses persistent inflammation, immunosuppression, and catabolism syndrome ^[2]. The same mediators that drive hyperinflammation also suppress adaptive effector immunity, which is why hyperinflammation and immunosuppression coexist rather than alternate.

Epidemiology¶

Burn-induced immune dysfunction underlies a heavy infectious burden. Severe burn injury carries an approximately 12% mortality rate driven by sepsis-induced organ failure, pneumonia, and other infections ^[11]. In a pediatric cohort of 287 patients, the prevalence of sepsis was 30% and of persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) was 15%, with PIICS occurring in roughly 1 in 6 children ^[8]. Pediatric burn patients have infectious complication rates as high as 71% ^[7]. The threshold for developing PIICS sits around 30 to 40% body surface area, with burns over 40% TBSA generally producing persistent critical illness ^[9]. Inhalation injury and larger TBSA are both strongly associated with sepsis and PIICS ^[8].

The susceptibility extends well beyond the index admission. A large cohort study found the burn population had twice the rate of infectious-disease hospital admissions and 3.5 times the hospital days of an uninjured cohort, plus a 1.75-fold greater rate of infectious-disease mortality over the 5 years after discharge ^[6]. These findings indicate that burn has long-lasting effects on immune function rather than a transient perturbation ^[6]. Globally, approximately 8.4 million people sustain burn injuries each year, leading to 110,000 deaths ^[20].

Pathophysiology¶

Biphasic immune response¶

Severe burn produces a defined trajectory: early (0 to 72 hours) hyperinflammation and damage-associated molecular pattern (DAMP) release, then a prolonged anti-inflammatory immunoparalysis ^[10,11]. The proinflammatory and anti-inflammatory imbalance, not inflammation alone, drives complications ^[10]. Genomic studies describe simultaneous up-regulation of inflammatory and compensatory anti-inflammatory programs and suppression of adaptive-immunity genes, with complications differing by magnitude and duration rather than a second hit ^[10].

Innate immunity: neutrophils¶

Burn impairs neutrophil bactericidal capacity early while paradoxically driving sustained neutrophilia and release of immature neutrophils ^[19]. Oxidative-burst suppression is durable: it remains depressed for months, with full recovery to control values first seen 3.5 months after the burn ^[18]. Modern work implicates dysregulated NETosis, with massive neutrophil extracellular trap release associated with lung injury when patients progress to infection ^[17].

Innate immunity: monocytes and macrophages¶

Macrophages are the central paradox of post-burn immunology: their production of interleukin-1, interleukin-6, and tumor necrosis factor alpha rises significantly after thermal injury even as they drive adaptive immunosuppression ^[85]. Reduced monocyte HLA-DR expression is one of the most reproducible human markers: it deepens with sepsis and predicts non-survival ^[12]. In-vitro exposure of postburn monocytes to interferon-gamma restores HLA Class II expression to control levels, and in-vivo re-expression of normal HLA Class II coincides with patient recovery ^[16]. Recent work describes a locus-specific epigenetic architecture programming macrophage immune and metabolic function after burn ^[29].

Innate immunity: dendritic cells, NK cells, complement¶

Dendritic cells are depleted and functionally impaired after burn, contributing to defective Th1 priming; circulating subsets fall and persistent depletion associates with sepsis ^[21,22]. NK cytotoxicity is depressed and NKG2D is downregulated, plausibly explaining herpesvirus susceptibility ^[23]. Complement shows early consumption followed by sustained activation that likely contributes to prolonged inflammation and impaired healing ^[24]. Mannose-binding lectin deficiency worsens Pseudomonas spread, with all MBL-null mice dying of septicemia after burn-site inoculation versus one-third of wild-type ^[25]. The NLRP3 inflammasome is upregulated after burn, and Nlrp3-null animals show 30% improved survival and better bacterial clearance ^[26].

Adaptive immunity: T-cell anergy and apoptosis¶

T-cell loss and dysfunction are the historical core of post-burn immunosuppression: CD3, CD4, and CD8 counts fall, with reduced mitogen responses, and the decline reflects both lymphopenia and intrinsic anergy, as cells show activation-marker expression yet fail to proliferate ^[30]. Apoptosis is a major driver; loss of lymphocytes, particularly T-cell apoptosis, is a central pathological event associated with susceptibility to life-threatening infection ^[31]. Patients who later develop T-cell anergy have increased T-cell apoptosis earlier in their course than patients who never become anergic ^[32].

Adaptive immunity: Th1-to-Th2 shift¶

Major injury drives a shift from Th1 toward Th2 dominance, with diminished interleukin-12 production and increased IL-4 and IL-10 ^[35]. In nonsurvivors the number of CD8+ IL-4-producing cells is significantly higher while interferon-gamma-releasing memory cells are lower than in survivors ^[36]. In-vivo IL-12 treatment restores Th1 function and decreased CLP mortality from 85% to 15% in burn animals ^[35].

Adaptive immunity: regulatory T cells¶

Treg expansion and enhanced suppressive potency are a major modern mechanism: human Tregs increase in potency after injury, rising from day 1 to day 7, and their depletion restores interferon-gamma and proliferation to control levels ^[37]. In mice, injury enhances Treg function as early as 7 days, restricted to injury-site-draining lymph nodes and mediated by surface TGF-beta1 ^[38]. Treg activation markers correlate with sepsis and fatal outcome ^[39].

Adaptive immunity: B cells and immunoglobulins¶

Humoral changes are biphasic and T-helper-dependent. Early IgG and IgM depression in the first postburn week recovers later, and restoration of IgM secretion to normal was achieved in only 60% of survivors at discharge ^[41]. In an experimental burn model, T-dependent antibody responses are suppressed for prolonged periods: thermal injury diminishes the ability to mount and maintain a normal IgG response despite normal or increased numbers of antigen-specific B cells, with a shift from IgM to IgG production ^[42]. The Th1-dependent isotype IgG2a is selectively reduced while Th2-dependent isotypes are spared; IL-10 neutralization restores the IgG2a response ^[43].

Immunosuppressive mediators¶

A web of soluble and cellular mediators links wound, neuroendocrine stress, and gut to systemic suppression. PGE is a central immunoregulatory mediator: inhibiting its production or neutralizing it with antibody prevents burn-induced suppression of cell-mediated immunity in animals ^[44]. IL-10 rises early and correlates with septic events; increased PBMC IL-10 production in the first 10 days correlates with subsequent sepsis ^[45], and systemic IL-10 relates to injury severity and complications ^[46]. DAMPs reprogram macrophages toward suppression; elevated day-1 heme corresponds to a 52% increase in odds of post-burn mortality ^[47], and HMGB1 is higher in patients who develop multiple organ dysfunction ^[48].

Assessment¶

No single biomarker defines post-burn immune status, but monocyte HLA-DR is the most validated. The percentage of HLA-DR-expressing monocytes falls markedly after severe burn, with a median of 31% at day 7 against 93% in healthy volunteers ^[12]. Every patient in one series presented with decreased monocyte HLA-DR at days 2 to 3; expression recovered from days 4 to 6 in survivors but stayed low in nonsurvivors, and persistent decrease was associated with mortality and septic complications ^[13]. HLA-DR on CD14+ monocytes falls further with the development of sepsis and serves as a useful monitoring parameter ^[14]. Sequential monitoring of HLA-DR on CD14+ cells carries prognostic significance, remaining persistently decreased in nonsurvivors ^[15]. Notably, plasma cytokines IL-6, TNF-alpha, and IL-10 provided no significant prognostic information in the same cohort where HLA-DR did ^[13], underscoring that functional markers outperform single static cytokine levels.

Lymphopenia carries strong prognostic weight. In a pediatric cohort, lymphopenia had the strongest association with septic events among laboratory and clinical criteria, so its presence should heighten concern for serious infection ^[8]. Functional ex-vivo assays add discrimination: children who developed nosocomial infection had lower LPS-induced TNF-alpha production capacity and lower monocyte counts and HLA-DR than those who did not ^[7]. Lower CD4+ counts and PHA-induced cytokine production capacity discriminate patients who develop infection, with IL-10 production capacity carrying high diagnostic value ^[49], and soluble CD27, BTLA, and TIM-3 are predictive of subsequent infectious complications ^[50]. Dynamic monitoring of leukocyte subsets tracks disease stage, with lymphocyte and monocyte counts lower and neutrophil and CRP values higher in nonsurvivors over the first postburn week ^[51].

A persistent methodologic caveat applies. Assessment of peripheral blood mononuclear cell function alone may not accurately reflect tissue-level immune status ^[52]. Findings from circulating-cell assays should be read with that limitation in mind.

Management¶

No immunomodulatory therapy has reached standard of care, and the gap between preclinical promise and clinical practice defines this area. Source-control and supportive principles have the firmest grounding. In animal models, early total wound excision restores cytotoxic T-lymphocyte function and survival in a burn-size-dependent manner ^[53,54], providing an immunologic rationale for expeditious wound excision ^[53]. Excision and skin grafting restored cell-mediated parameters toward normal, consistent with burned tissue itself suppressing cellular immunity ^[55]. The picture is not uniform: a classic study found very early excision did not alter the immunosuppression that follows severe thermal trauma ^[56], and late necrectomy cannot prevent suppression and may itself worsen immunologic status ^[57].

The preclinical pharmacology is broad and mostly unconfirmed in humans. Anti-IL-10 antibody given at 1 day after injury improved CLP survival in mice, while delaying treatment 3 days lost the benefit ^[58]. Low-dose IL-12 improved survival after CLP ^[27]. Anti-TNF antibody improved outcome only when timed to peak TNF production at day 7 ^[59]. Anti-PD-L1 antibody improved bacterial clearance and survival during Pseudomonas burn wound infection ^[28]. These findings establish targets, not treatments; their human translation remains unproven, and timing dependence is a recurring theme. Glucocorticoid use illustrates the risk: hydrocortisone administration may worsen the immunosuppression associated with severe injury ^[60].

Complications¶

The downstream consequence of immune failure is infection and its sequelae. Burn-induced immunosuppression increases susceptibility to infection and predisposes to systemic inflammatory response syndrome and sepsis ^[61]. Immunosuppression after burn raises the risk of sepsis and multiple organ failure ^[62]. T-cell apoptosis at the intestinal barrier can lead to failure of the immunological barrier and increased risk of sepsis ^[63]. Patients are particularly vulnerable to opportunistic and viral infection: reduced NKG2D expression helps explain susceptibility to herpesviruses ^[23], and herpes simplex activation in severe burn is associated with longer mechanical ventilation and hospital stay ^[64]. Viral infections, though less common than bacterial ones, occur in the more severely burned and carry poor outcomes ^[65]. Fungal infection is a major complication, with disseminated mucormycosis carrying an 80% mortality versus 36% for localized disease ^[66].

Special Considerations¶

Age, sex, and exposures modify the depth and duration of suppression. Burn injury causes greater suppression of mesenteric lymph node T-cell proliferation and a more pronounced Th2 shift in aged mice than in young ^[33]. In aged animals, estrogen supplementation before injury partially recovered the delayed-type hypersensitivity response and improved survival from 42% to 70% ^[34]. Sex differences operate through estradiol: cell-mediated immunity was suppressed in female but not male mice 10 days after burn, mediated in part by IL-6 ^[67].

Alcohol exposure compounds the injury. Acute ethanol exposure is linked with increased susceptibility to infection and increased mortality in trauma and burn patients ^[68], and the combination of alcohol and burn produces immune suppression greater in magnitude and duration than either insult alone ^[69]. Pediatric patients carry a distinct profile, with diminished antibody responses to diphtheria, tetanus, and pertussis vaccine antigens after burn, demonstrating a lasting change in the immune profile of pediatric survivors ^[70].

Outcomes¶

Immune trajectory predicts survival. In survivors, T-lymphocyte numbers return gradually toward normal ^[72], and immune parameters tend to normalize by the third postburn week ^[73]. Persistent defects mark a worse course: a later increase in suppressor-cell activity beyond 14 days postburn correlates closely with mortality from sepsis ^[74], and patients whose antibody response stayed suppressed developed fatal septicemia ^[71]. The relationship is graded; patients whose T cells progressed to severe dysfunction had multiple organ failure with 80% mortality, while those with milder responses had positive outcomes ^[76].

The morbidity is long-lasting. Burn survivors face elevated risk of hospital admission for infection, mental health conditions, cardiovascular disease, and cancer for years after the injury, and CD8+ T-cell-mediated immunity may remain dysfunctional for a sustained period even after non-severe burn ^[75]. Disseminated fungal infection illustrates the lethality of the immunocompromised state, with 80% mortality in disseminated versus 36% in localized mucormycosis ^[66].

Controversies and Evidence Gaps¶

The literature carries several genuine disagreements that a careful reader should hold in view.

Dendritic cell suppression is contested. Human and clinical data support DC depletion and functional impairment ^[21,22], but a murine splenic-DC study concluded that DCs do not acquire a suppressive phenotype after severe injury in mice ^[78]. The dysfunction is best framed as compartment-, species-, and subset-specific rather than universal.

Treg directionality conflicts. Most data show Treg expansion and enhanced potency ^[37,39], but at least one human study found decreased peripheral Treg percentages after extensive burn ^[40]. The discrepancy is likely a sampling-compartment or timepoint artifact, and uniform expansion should not be asserted.

The Th2 shift is not universal. Burn can prime naive CD4 T cells toward increased interferon-gamma ^[79], and the shift is antigen-dependent in transgenic models ^[80], qualifying the obligate-Th2 narrative.

PGE2 differs in vitro versus in vivo. PGE2 is potently immunosuppressive in vitro, but data indicate it may not be as immunosuppressive in in-vivo models as in-vitro work suggests ^[81]. The discrepancy should be stated rather than resolved.

Modern mechanisms are thin and recent. Findings on NETs, the inflammasome, and epigenetic macrophage programming rest on relatively few, largely 2017 to 2026, often animal or transcriptomic studies. New work challenges the classical view that burn immune suppression is purely a consequence of systemic inflammation, proposing durable epigenetically programmed alterations in macrophage function ^[77].

The inflammatory response may sometimes help. Some data suggest the inflammatory response following burn may be beneficial to the immune system ^[82], and that the counterinflammatory response may occasionally benefit the host ^[83], cautioning against viewing all post-burn inflammation as harmful.

Animal-model weighting. Much of the mechanistic literature leans on rodent data, and the question of whether animal splenic-lymphocyte studies correlate with human circulating-blood studies is explicitly raised ^[84]. Human-specific anchors such as HLA-DR, IL-10, Treg potency, and apoptosis should carry the most weight for clinical inference.

References¶

[1] Kawakami M, Okada Y. "[Immunological alterations after extensive burn injury]." Nihon Geka Gakkai zasshi 1998. PMID: 9547744 ↩

[2] Osuka A, Shigeno A, Matsuura H, Onishi S, Yoneda K. "Systemic immune response of burns from the acute to chronic phase." Acute medicine & surgery 2024. PMID: 38894736 ↩

[3] Gelfand JA. "Infections in burn patients: a paradigm for cutaneous infection in the patient at risk." The American journal of medicine 1984. PMID: 6372465 ↩

[4] Baker CC, Yamada AH, Faist E, Kupper TS. "Interleukin-1 and T cell function following injury." The Journal of burn care & rehabilitation 1987. PMID: 2963826 ↩

[5] Beckmann N, Huber F, Hanschen M, St Pierre Schneider B, Nomellini V, Caldwell CC. "Scald Injury-Induced T Cell Dysfunction Can Be Mitigated by Gr1+ Cell Depletion and Blockage of CD47/CD172a Signaling." Frontiers in immunology 2020. PMID: 32477354 ↩

[6] Duke JM, Randall SM, Wood FM, Boyd JH, Fear MW. "Burns and long-term infectious disease morbidity: A population-based study." Burns : journal of the International Society for Burn Injuries 2017. PMID: 28041752 ↩

[7] Thakkar RK et al. "Measures of Systemic Innate Immune Function Predict the Risk of Nosocomial Infection in Pediatric Burn Patients." Journal of burn care & research : official publication of the American Burn Association 2021. PMID: 33128368 ↩

[8] Santarelli MD et al. "Persistent inflammation, immunosuppression, and catabolism syndrome and sepsis in pediatric burns." Burns : journal of the International Society for Burn Injuries 2025. PMID: 40555121 ↩

[9] Berger MM, Koekkoek KW, Montoro L, Pantet O. "What does 'PICS' mean in major burns? Persistent critical illness or post-intensive care syndrome." Burns : journal of the International Society for Burn Injuries 2026. PMID: 41946293 ↩

[10] Xiao W et al. "A genomic storm in critically injured humans." The Journal of experimental medicine 2011. PMID: 22110166 ↩

[11] Willis ML et al. "Plasma extracellular vesicles released after severe burn injury modulate macrophage phenotype and function." Journal of leukocyte biology 2022. PMID: 34342045 ↩

[12] Sachse C, Prigge M, Cramer G, Pallua N, Henkel E. "Association between reduced human leukocyte antigen (HLA)-DR expression on blood monocytes and increased plasma level of interleukin-10 in patients with severe burns." Clinical chemistry and laboratory medicine 1999. PMID: 10353460 ↩

[13] Venet F et al. "Decreased monocyte human leukocyte antigen-DR expression after severe burn injury: Correlation with severity and secondary septic shock." Critical care medicine 2007. PMID: 17568330 ↩

[14] Yang HM, Yu Y, Chai JK, Hu S, Sheng ZY, Yao YM. "Low HLA-DR expression on CD14+ monocytes of burn victims with sepsis, and the effect of carbachol in vitro." Burns : journal of the International Society for Burn Injuries 2008. PMID: 18538934 ↩

[15] Dong N, Jin BQ, Yao YM, Yu Y, Sheng ZY. "[The relationship between dysfunction of cell-mediated immunity and prognosis in severely burned patients]." Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 2008. PMID: 18786305 ↩

[16] Gibbons RA, Martinez OM, Lim RC, Horn JK, Garovoy MR. "Reduction in HLA-DR, HLA-DQ and HLA-DP expression by Leu-M3+ cells from the peripheral blood of patients with thermal injury." Clinical and experimental immunology 1989. PMID: 2495202 ↩

[17] Xie C et al. "Targeted nuclear degranulation of neutrophils in the shock stage of severe burns drives rapid neutrophil extracellular trap release during infection to mediate acute lung injury." Free radical biology & medicine 2026. PMID: 41371002 ↩

[18] Parment K, Zetterberg A, Ernerudh J, Bakteman K, Steinwall I, Sjoberg F. "Long-term immunosuppression in burned patients assessed by in vitro neutrophil oxidative burst (Phagoburst)." Burns : journal of the International Society for Burn Injuries 2007. PMID: 17537580 ↩

[19] Mulder PPG et al. "Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles." Frontiers in immunology 2020. PMID: 33584717 ↩

[20] Khalaf F, Wojtowicz-Piotrowski S, Ricciuti Z, Dadashizadeh G, Barayan D, Jeschke MG. "Endocrine disruptions in thermal injuries: exploring immune system interactions." Physiological reviews 2026. PMID: 41973596 ↩

[21] Bae L, Bohannon JK, Cui W, Vinish M, Toliver-Kinsky T. "Fms-like tyrosine kinase-3 ligand increases resistance to burn wound infection through effects on plasmacytoid dendritic cells." BMC immunology 2017. PMID: 28228109 ↩

[22] D'Arpa A et al. "Decrease of circulating dendritic cells in burn patients." Annals of burns and fire disasters 2007. PMID: 21991097 ↩

[23] Haik J et al. "Increased serum NKG2D-ligands and downregulation of NKG2D in peripheral blood NK cells of patients with major burns." Oncotarget 2016. PMID: 26745675 ↩

[24] Mulder PPG, van Hooren M, Bumbuc RV, Hooijmans CR, Korkmaz HI, Boekema BKHL. "Complement response to burn injury: systematic review and meta-analysis of patient and animal studies." Frontiers in immunology 2026. PMID: 41822479 ↩

[25] Møller-Kristensen M et al. "Deficiency of mannose-binding lectin greatly increases susceptibility to postburn infection with Pseudomonas aeruginosa." Journal of immunology (Baltimore, Md. : 1950) 2006. PMID: 16424207 ↩

[26] Stanojcic M, Vinaik R, Abdullahi A, Chen P, Jeschke MG. "NLRP3 knockout enhances immune infiltration and inflammatory responses and improves survival in a burn sepsis model." Immunology 2022. PMID: 34773253 ↩

[27] Göebel A et al. "Injury induces deficient interleukin-12 production, but interleukin-12 therapy after injury restores resistance to infection." Annals of surgery 2000. PMID: 10674618 ↩

[28] Patil NK, Luan L, Bohannon JK, Hernandez A, Guo Y, Sherwood ER. "Frontline Science: Anti-PD-L1 protects against infection with common bacterial pathogens after burn injury." Journal of leukocyte biology 2018. PMID: 29345058 ↩

[29] Kim HG et al. "Chromatin Remodeling and Transcriptional Silencing Define the Dynamic Innate Immune Response of Tissue Resident Macrophages After Burn Injury." bioRxiv : the preprint server for biology 2025. PMID: 40475502 ↩

[30] Teodorczyk-Injeyan JA, Cembrzynska-Nowak M, Lalani S, Peters WJ, Mills GB. "Immune deficiency following thermal trauma is associated with apoptotic cell death." Journal of clinical immunology 1995. PMID: 8576318 ↩

[31] Roth S et al. "Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade." Immunity 2021. PMID: 33667383 ↩

[32] Pellegrini JD, De AK, Kodys K, Puyana JC, Furse RK, Miller-Graziano C. "Relationships between T lymphocyte apoptosis and anergy following trauma." The Journal of surgical research 2000. PMID: 10644489 ↩

[33] Choudhry MA, Plackett TP, Schilling EM, Faunce DE, Gamelli RL, Kovacs EJ. "Advanced age negatively influences mesenteric lymph node T cell responses after burn injury." Immunology letters 2003. PMID: 12644320 ↩

[34] Kovacs EJ, Plackett TP, Witte PL. "Estrogen replacement, aging, and cell-mediated immunity after injury." Journal of leukocyte biology 2004. PMID: 14761938 ↩

[35] O'Sullivan ST, Lederer JA, Horgan AF, Chin DH, Mannick JA, Rodrick ML. "Major injury leads to predominance of the T helper-2 lymphocyte phenotype and diminished interleukin-12 production associated with decreased resistance to infection." Annals of surgery 1995. PMID: 7574928 ↩

[36] Zedler S, Bone RC, Baue AE, von Donnersmarck GH, Faist E. "T-cell reactivity and its predictive role in immunosuppression after burns." Critical care medicine 1999. PMID: 9934895 ↩

[37] MacConmara MP et al. "Increased CD4+ CD25+ T regulatory cell activity in trauma patients depresses protective Th1 immunity." Annals of surgery 2006. PMID: 16998360 ↩

[38] Ni Choileain N, MacConmara M, Zang Y, Murphy TJ, Mannick JA, Lederer JA. "Enhanced regulatory T cell activity is an element of the host response to injury." Journal of immunology (Baltimore, Md. : 1950) 2006. PMID: 16365414 ↩

[39] Huang LF, Yao YM, Dong N, Yu Y, He LX, Sheng ZY. "Association between regulatory T cell activity and sepsis and outcome of severely burned patients: a prospective, observational study." Critical care (London, England) 2010. PMID: 20064232 ↩

[40] Zhang ZJ, Ding LT, Zou J, Lyu GZ. "[Changes of helper T lymphocytes 17 and regulatory T lymphocytes in peripheral blood of patients with extensive burn at early stage in August 2nd Kunshan factory aluminum dust explosion accident and the significance]." Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns 2018. PMID: 29961293 ↩

[41] Teodorczyk-Injeyan JA, Sparkes BG, Peters WJ. "Regulation of IgM production in thermally injured patients." Burns : journal of the International Society for Burn Injuries 1989. PMID: 2527518 ↩

[42] Molloy RG, Nestor M, Collins KH, Holzheimer RG, Mannick JA, Rodrick ML. "The humoral immune response after thermal injury: an experimental model." Surgery 1994. PMID: 8128358 ↩

[43] Kelly JL, Lyons A, Soberg CC, Mannick JA, Lederer JA. "Anti-interleukin-10 antibody restores burn-induced defects in T-cell function." Surgery 1997. PMID: 9288117 ↩

[44] Freeman TR, Shelby J. "Effect of anti-PGE antibody on cell-mediated immune response in thermally injured mice." The Journal of trauma 1988. PMID: 3346917 ↩

[45] Lyons A, Kelly JL, Rodrick ML, Mannick JA, Lederer JA. "Major injury induces increased production of interleukin-10 by cells of the immune system with a negative impact on resistance to infection." Annals of surgery 1997. PMID: 9351713 ↩

[46] Köller M, Clasbrummel B, Kollig E, Hahn MP, Muhr G. "Major injury induces increased production of interleukin-10 in human granulocyte fractions." Langenbeck's archives of surgery 1998. PMID: 9921948 ↩

[47] Tullie S et al. "Severe thermal and major traumatic injury results in elevated plasma concentrations of total heme that are associated with poor clinical outcomes and systemic immune suppression." Frontiers in immunology 2024. PMID: 38947312 ↩

[48] Dong N et al. "[Change in T cell-mediated immunity and its relationship with high mobility group box-1 protein levels in extensively burned patients]." Zhonghua wai ke za zhi [Chinese journal of surgery] 2008. PMID: 18953932 ↩

[49] Thakkar RK et al. "Measures of Adaptive Immune Function Predict the Risk of Nosocomial Infection in Pediatric Burn Patients." Journal of burn care & research : official publication of the American Burn Association 2022. PMID: 35436346 ↩

[50] Penatzer JA et al. "Early detection of soluble CD27, BTLA, and TIM-3 predicts the development of nosocomial infection in pediatric burn patients." Frontiers in immunology 2022. PMID: 35958579 ↩

[51] Zhi L, Wang X, Pan X, Han C. "The asynchronous dynamic changes and interrelationships between leukocyte composition and inflammatory markers and potential clinical significance in the early stage and sepsis stage in severe burns." Burns : journal of the International Society for Burn Injuries 2024. PMID: 38724345 ↩

[52] Schwacha MG, Schneider CP, Chaudry IH. "Differential expression and tissue compartmentalization of the inflammatory response following thermal injury." Cytokine 2002. PMID: 12027408 ↩

[53] Hultman CS, Yamamoto H, deSerres S, Frelinger JA, Meyer AA. "Early but not late burn wound excision partially restores viral-specific T lymphocyte cytotoxicity." The Journal of trauma 1997. PMID: 9314305 ↩

[54] Hultman CS, Cairns BA, deSerres S, Frelinger JA, Meyer AA. "Early, complete burn wound excision partially restores cytotoxic T lymphocyte function." Surgery 1995. PMID: 7638760 ↩

[55] Cetinkale O, Ulualp KM, Ayan F, Düren M, Cizmeci O, Pusane A. "Early wound excision and skin grafting restores cellular immunity after severe burn trauma." The British journal of surgery 1993. PMID: 8242303 ↩

[56] Jacobson BK, Baker CC. "Immunosuppression following excision of burn eschar and syngeneic grafting in major thermal trauma." The Yale journal of biology and medicine 1984. PMID: 6240833 ↩

[57] Vrsanský P, Janota S. "Immunological consequences of burn injury in children." European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie 1995. PMID: 7756234 ↩

[58] Lyons A, Goebel A, Mannick JA, Lederer JA. "Protective effects of early interleukin 10 antagonism on injury-induced immune dysfunction." Archives of surgery (Chicago, Ill. : 1960) 1999. PMID: 10593329 ↩

[59] O'Riordain MG, O'Riordain DS, Molloy RG, Mannick JA, Rodrick ML. "Dosage and timing of anti-TNF-alpha antibody treatment determine its effect of resistance to sepsis after injury." The Journal of surgical research 1996. PMID: 8806480 ↩

[60] Plassais J et al. "Transcriptome modulation by hydrocortisone in severe burn shock: ancillary analysis of a prospective randomized trial." Critical care (London, England) 2017. PMID: 28623938 ↩

[61] Bhat S, Milner S. "Antimicrobial peptides in burns and wounds." Current protein & peptide science 2007. PMID: 17979765 ↩

[62] Yabuki T et al. "CpG oligonucleotides activate the immune response in burned mice." The Journal of surgical research 2010. PMID: 19540526 ↩

[63] Woodside KJ et al. "Decreased lymphocyte apoptosis by anti-tumor necrosis factor antibody in Peyer's patches after severe burn." Shock (Augusta, Ga.) 2003. PMID: 12813372 ↩

[64] Sen S, Szoka N, Phan H, Palmieri T, Greenhalgh D. "Herpes simplex activation prolongs recovery from severe burn injury and increases bacterial infection risk." Journal of burn care & research : official publication of the American Burn Association 2012. PMID: 22079915 ↩

[65] Kiley JL, Chung KK, Blyth DM. "Viral Infections in Burns." Surgical infections 2021. PMID: 32460632 ↩

[66] Dang J et al. "Mucormycosis following burn injuries: A systematic review." Burns : journal of the International Society for Burn Injuries 2023. PMID: 35842270 ↩

[67] Gregory MS, Duffner LA, Faunce DE, Kovacs EJ. "Estrogen mediates the sex difference in post-burn immunosuppression." The Journal of endocrinology 2000. PMID: 10657848 ↩

[68] Rendon JL, Janda BA, Bianco ME, Choudhry MA. "Ethanol exposure suppresses bone marrow-derived dendritic cell inflammatory responses independent of TLR4 expression." Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 2012. PMID: 22812678 ↩

[69] Messingham KA, Faunce DE, Kovacs EJ. "Alcohol, injury, and cellular immunity." Alcohol (Fayetteville, N.Y.) 2002. PMID: 12551755 ↩

[70] Johnson BZ et al. "Pediatric Burn Survivors Have Long-Term Immune Dysfunction With Diminished Vaccine Response." Frontiers in immunology 2020. PMID: 32793203 ↩

[71] Teodorczyk-Injeyan JA, Sparkes BG, Falk RE, Peters WJ. "Polyclonal immunoglobulin production in burned patients--kinetics and correlations with T-cell activity." The Journal of trauma 1986. PMID: 2943903 ↩

[72] Wood GW, Volenec FJ, Mani MM, Humphrey LJ. "Dynamics of T-lymphocyte subpopulations and T-lymphocyte function following thermal injury." Clinical and experimental immunology 1978. PMID: 306326 ↩

[73] Daniels JC, Sakai H, Ritzmann SE. "Lymphoid response of the burn patient." Southern medical journal 1975. PMID: 1099652 ↩

[74] McIrvine AJ, O'Mahony JB, Saporoschetz I, Mannick JA. "Depressed immune response in burn patients: use of monoclonal antibodies and functional assays to define the role of suppressor cells." Annals of surgery 1982. PMID: 6214221 ↩

[75] Barrett LW et al. "Non-severe burn injury increases cancer incidence in mice and has long-term impacts on the activation and function of T cells." Burns & trauma 2022. PMID: 35505970 ↩

[76] De AK, Kodys K, Puyana JC, Fudem G, Pellegrini J, Miller-Graziano CL. "Only a subset of trauma patients with depressed mitogen responses have true T cell dysfunctions." Clinical immunology and immunopathology 1997. PMID: 9000045 ↩

[77] Kim HG et al. "Chromatin Remodeling and Transcriptional Silencing Define the Dynamic Innate Immune Response of Tissue Resident Macrophages After Burn Injury." Shock (Augusta, Ga.) 2026. PMID: 41166121 ↩

[78] Fujimi S et al. "Murine dendritic cell antigen-presenting cell function is not altered by burn injury." Journal of leukocyte biology 2009. PMID: 19228816 ↩

[79] Kavanagh EG, Kelly JL, Lyons A, Soberg CC, Mannick JA, Lederer JA. "Burn injury primes naive CD4+ T cells for an augmented T-helper 1 response." Surgery 1998. PMID: 9706148 ↩

[80] Guo Z et al. "Burn injury promotes antigen-driven Th2-type responses in vivo." Journal of immunology (Baltimore, Md. : 1950) 2003. PMID: 14530317 ↩

[81] Waymack JP, Yurt RW. "Effect of prostaglandin E on immune function in multiple animal models." Archives of surgery (Chicago, Ill. : 1960) 1988. PMID: 3263107 ↩

[82] Jobin N, Garrel DR, Bernier J. "Increased burn-induced immunosuppression in lipopolysaccharide-resistant mice." Cellular immunology 2000. PMID: 10753497 ↩

[83] Zang Y et al. "Burn injury initiates a shift in superantigen-induced T cell responses and host survival." Journal of immunology (Baltimore, Md. : 1950) 2004. PMID: 15067067 ↩

[84] Deitch EA, Xu DZ, Qi L. "Different lymphocyte compartments respond differently to mitogenic stimulation after thermal injury." Annals of surgery 1990. PMID: 2294848 ↩

[85] O'Riordain MG, Collins KH, Pilz M, Saporoschetz IB, Mannick JA, Rodrick ML. "Modulation of macrophage hyperactivity improves survival in a burn-sepsis model." Archives of surgery (Chicago, Ill. : 1960) 1992. PMID: 1540091 ↩