title: Molecular mechanisms of decreased interleukin-2 production after thermal injury.
abstract: BACKGROUND
  Among the fundamental immunologic abnormalities induced by serious traumatic or thermal injury are alterations in T cell activation, reduced lymphocyte interleukin-2 (IL-2) production, and associated depression of T lymphocyte proliferation. This study attempts to localize the cellular mechanisms underlying abnormal IL-2 production in thermal injury.
  
  
  METHODS
  Following National Institutes of Health guidelines, 150 A/J mice were anesthetized, subjected to a 20% full-thickness scald burn injury or sham burn, and killed at intervals from 4 to 21 days later; splenocytes were harvested for in vitro studies. For measurement of IL-2 production, cells were cultured with either concanavalin A or a combination of the phorbol ester PMA, which directly activates protein kinase C, and the calcium ionophore A23187, which increases intracellular calcium. Cytokine mRNA expression was measured by Northern blot analysis and IL-2 production by bioassay.
  
  
  RESULTS
  Both IL-2 production and IL-2 mRNA expression were consistently suppressed in concanavalin A-stimulated cells from burned mice compared with sham burns. This suppression of IL-2 and IL-2 mRNA also occurred when T cells were activated with PMA and A23187, bypassing the earlier stages of the signal transduction mechanism. IL-1 beta and tumor necrosis factor-alpha mRNA expression were consistently increased in burned animals, indicating that decreased IL-2 mRNA expression was specific to IL-2 and not representative of a global decrease in cytokine mRNA expression.
  
  
  CONCLUSIONS
  These results suggest that the principal cellular abnormalities that result in altered T cell activation and IL-2 production after thermal injury lie downstream of the initiating signal transduction events and before IL-2 gene transcription.
authors.affiliation: Department of Surgery, Harvard Medical School, Brigham and Women's Hospital, Boston, Mass. 02115.
authors.forename: D S
authors.initials: DS
authors.lastname: O'Riordain
authors.forename: M V
authors.initials: MV
authors.lastname: Mendez
authors.forename: M G
authors.initials: MG
authors.lastname: O'Riordain
authors.forename: R G
authors.initials: RG
authors.lastname: Molloy
authors.forename: R G
authors.initials: RG
authors.lastname: Holzheimer
authors.forename: K
authors.initials: K
authors.lastname: Collins
authors.forename: I
authors.initials: I
authors.lastname: Saporoschetz
authors.forename: J A
authors.initials: JA
authors.lastname: Mannick
authors.forename: M L
authors.initials: ML
authors.lastname: Rodrick
mesh_terms: D000818:Animals; D002056:Burns / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D007375:Interleukin-1; D007376:Interleukin-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate