GROWTH-HORMONE IMPROVES THE RESISTANCE OF THERMALLY INJURED MICE INFECTED WITH HERPES-SIMPLEX VIRUS TYPE

Background: Growth hormone (GH) has been shown to promote wound healin g and to improve protein metabolism in burned patients. Through immuno modulation, GH has also protected rats infected with Salmonella typhim urium and mice infected with Escherichia coli. In spite of advances in the management of patient care for those with thermal injuries, high mortality rates of burned patients as a result of infections are of sp ecial concern. An improvement in the resistance of burned patients to certain infections will make the beneficial role of GH very clear. In this study, therefore, the immunomodulating effects of recombinant hum an GH (rhGH) in thermally injured mice exposed to opportunistic herpes virus infections were investigated. Methods: (1) Burned mice, exposed to herpes simplex virus ape 1 (HSV-1), were treated subcutaneously wit h rhGH (4 mg/kg) and observed for 21 days to determine the protective antiviral effect of rhGH. (2) Because of reports describing a lack of interferon-gamma (IFN-gamma) responsiveness in burned mice, the IFN-ga mma-producing ability of the splenic mononuclear cells (SMNC) from bur ned mice treated with rhGH was examined. (3) Because the generation of burn-associated suppressor macrophages that can inhibit the IFN-gamma production by SR INC has been previously described, the suppressor ce ll activities of macrophages from burned mice treated with rhGH mere e xamined. Results: After exposure to lethal amounts of HSV-1, mice trea ted with rhGH displayed a reduced mortality rate compared with control mice treated with saline. SMNC from burned mice treated with rhGH pro duced IFN-gamma, whereas this cytokine was not produced by SMNC from b urned mice treated with saline. Also, an inhibition of the generation of burn-associated suppressor macrophages was displayed in burned mice treated with rhGH. Conclusion: Exogenous administration of rhGH cause d an improvement in the resistance of burned mice to HSV-1 infection. In burned mice treated with rhGH, the impaired IFN-gamma responsivenes s was restored and the generation of burn-associated suppressor macrop hages was inhibited. IFN-gamma, a typical antiviral cytokine induced b y rhGH through the regulation of the suppressor macrophage generation, may therefore play a role in the protection of burned mice infected w ith a lethal amount of HSV-1.