title: Insulin-like growth factor-I/insulin-like growth factor binding protein-3 alters lymphocyte responsiveness following severe burn.
abstract: OBJECTIVE
  Following severe burn, patients are immunocompromised, making them at increased risk for infection. Exogenous growth hormone has been shown to partially restore immune function. Herein, we investigated Th1/Th2 cytokine profiles and cellular proliferation in isolated mononuclear cells after treatment with exogenous insulin-like growth factor-I (IGF-I), the indirect mediator of many growth hormone effects, in severely burned patients.
  
  
  METHODS
  Eight children and 2 adults with >20% total body surface area burns were prospectively randomized to receive either placebo or 4 mg/kg rhIGF-I/IGFBP-3 for one-week intervals (2 groups), with another group receiving placebo for both cycles. Normal children were examined for comparison. Isolated whole blood lymphocyte production of Th1 (IL-2, IFN-gamma) and Th2 (IL-4, IL-10) cytokines, and proliferative responses to specific T-cell mitogens were measured.
  
  
  RESULTS
  Depressed Th1 and exaggerated Th2 cytokine responses were seen in all burned subjects compared to non-burned controls (P < 0.05). IL-2 and IFN-gamma production increased in patients treated with IGF-I/IGFBP-3 (P < 0.05). IL-4 production significantly decreased, while IL-10 levels did not change. Cytokine production did not change in those receiving two courses of placebo. Proliferative responses of isolated mononuclear cells to IL-2 as a Th1 specific mitogen increased with IGF-I/IGFBP-3 treatment (P < 0.05).
  
  
  CONCLUSIONS
  Following severe burn, a shift occurs toward a predominant Th2 phenotype. Exogenous IGF-I/IGFBP-3 treatment partially reverses this response.
authors.affiliation: Shriners Hospitals for Children, 815 Market Street, Galveston, TX 77550-2725, USA. swolf@utmb.edu
authors.forename: Steven E
authors.initials: SE
authors.lastname: Wolf
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Woodside
authors.forename: Roque J
authors.initials: RJ
authors.lastname: Ramirez
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Fujio
authors.initials: F
authors.lastname: Suzuki
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
mesh_terms: D000293:Adolescent; D000328:Adult; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D006801:Humans; D007275:Injections, Intravenous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000627:therapeutic use; D015847:Interleukin-4 / Q000096:biosynthesis; D008214:Lymphocytes / Q000187:drug effects*; D008875:Middle Aged; D010641:Phenotype; D011994:Recombinant Proteins / Q000008:administration & dosage; D013601:T-Lymphocytes
chemical_list: D004338:Drug Combinations; D018972:Insulin-Like Growth Factor Binding Protein 3; D007376:Interleukin-2; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma