Insulin-like growth factor-I/insulin-like growth factor binding protein-3 alters lymphocyte responsiveness following severe burn

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-γ) 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-γ 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.