title: Genetic variability in the immune-inflammatory response after major burn injury.
abstract: Thermal injury induces immune dysfunction and alters numerous physiological parameters. Studies have proposed that genetics influence the outcome after traumatic injury and/or sepsis, however, the contribution of genetics to the immune-inflammatory response postburn has not been investigated. In this study, mice of three distinct genetic backgrounds (C57BL/6NCrlBR, BALB/cAnNCrlBR, and 129S6/SvEvTac) were subjected to thermal injury or a sham procedure, and 3 days later, blood and splenic immune cells (splenocytes and macrophages) were isolated for analysis. Splenocytes from the C57BL/6NCrlBR strain displayed suppressed splenic T cell proliferation postinjury, whereas the other strains were unaffected. Burn injury also induced a shift toward a Th2-type T-cell response (suppressed IFN-gamma production) in the C57BL/6NCrlBR strain, but not in the other strains. Macrophages from C57BL/6NCrlBR and 129S6/SvEvTac mice were highly proinflammatory with elevated productive capacity for TNF-alpha and nitric oxide, whereas no such changes were observed in macrophages for BALB/cNCrlBR mice. C57BL/6NCRLBR macrophages produced increased IL-10 levels postburn, and BALB/cNCrlBR macrophages had suppressed IL-10 production postinjury. No differences in fasting blood glucose and insulin were observed after thermal injury. However, significant postburn weight loss was observed in the BALB/cNCrlBR and 129S6/SvEvTac strains, but not in the C57BL/6NCrlBR strain. In summary, these findings support the concept that the immune-inflammatory response postburn is influenced by genetic make-up. Further elucidation of the influence of genetics under such conditions is likely to contribute to the improvement in existing, and development of new, therapeutic regimes for burn patients.
authors.affiliation: Department of Surgery Center for Surgical Research, G094 Volker Hall, University of Alabama, 1670 University Boulevard, Birmingham, AL 35294, USA. schwacha@uab.edu
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
authors.forename: Lawanda T
authors.initials: LT
authors.lastname: Holland
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Messina
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002056:Burns / Q000276:immunology*; D017252:CD3 Complex / Q000096:biosynthesis; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D005947:Glucose / Q000378:metabolism; D006358:Hot Temperature; D007107:Immune System; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D007328:Insulin / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D018417:Th1 Cells; D018418:Th2 Cells; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D017252:CD3 Complex; D016207:Cytokines; D007328:Insulin; D007376:Interleukin-2; D016753:Interleukin-10; D009569:Nitric Oxide; D005947:Glucose