Insulin-like growth factor-I/insulin-like growth factor binding protein-3 alters lymphocyte responsiveness following severe burn.
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.
Wolf
Steven E
SE
Shriners Hospitals for Children, 815 Market Street, Galveston, TX 77550-2725, USA. swolf@utmb.edu
Woodside
Kenneth J
KJ
Ramirez
Roque J
RJ
Kobayashi
Makiko
M
Suzuki
Fujio
F
Herndon
David N
DN
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
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