Growth hormone improves the resistance of thermally injured mice infected with herpes simplex virus type 1.
BACKGROUND
Growth hormone (GH) has been shown to promote wound healing and to improve protein metabolism in burned patients. Through immunomodulation, GH has also protected rats infected with Salmonella typhimurium 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 special 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 human GH (rhGH) in thermally injured mice exposed to opportunistic herpesvirus infections were investigated.


METHODS
(1) Burned mice, exposed to herpes simplex virus type 1 (HSV-1), were treated subcutaneously with 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-gamma-producing ability of the splenic mononuclear cells (SMNC) from burned mice treated with rhGH was examined. (3) Because the generation of burn-associated suppressor macrophages that can inhibit the IFN-gamma production by SMNC has been previously described, the suppressor cell activities of macrophages from burned mice treated with rhGH were examined.


RESULTS
After exposure to lethal amounts of HSV-1, mice treated with rhGH displayed a reduced mortality rate compared with control mice treated with saline. SMNC from burned mice treated with rhGH produced IFN-gamma, whereas this cytokine was not produced by SMNC from burned mice treated with saline. Also, an inhibition of the generation of burn-associated suppressor macrophages was displayed in burned mice treated with rhGH.


CONCLUSIONS
Exogenous administration of rhGH caused an improvement in the resistance of burned mice to HSV-1 infection. In burned mice treated with rhGH, the impaired IFN-gamma responsiveness was restored and the generation of burn-associated suppressor macrophages was inhibited. IFN-gamma, a typical antiviral cytokine induced by rhGH through the regulation of the suppressor macrophage generation, may therefore play a role in the protection of burned mice infected with a lethal amount of HSV-1.
Takagi
K
K
Shriners Burns Institute, Department of Surgery, University of Texas Medical Branch, Galveston 77555-0835, USA.
Suzuki
F
F
Barrow
R E
RE
Wolf
S E
SE
Kobayashi
M
M
Herndon
D N
DN
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D002056:Burns / Q000150:complications* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D013006:Growth Hormone / Q000276:immunology / Q000627:therapeutic use*; D006561:Herpes Simplex / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D013154:Spleen / Q000276:immunology; D014945:Wound Healing / Q000187:drug effects; D014946:Wound Infection / Q000209:etiology / Q000276:immunology / Q000628:therapy*
D000276:Adjuvants, Immunologic; D007371:Interferon-gamma; D013006:Growth Hormone