PURPOSE: 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.
RCT Entities:
PURPOSE: 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: Alan E Rosenbach; Piyush Koria; Jeremy Goverman; Kenneth T Kotz; Amit Gupta; Ming Yu; Shawn P Fagan; Daniel Irimia; Ronald G Tompkins Journal: Clin Transl Sci Date: 2011-02 Impact factor: 4.689
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