The Effect of Growth Hormone on TNF-alpha Level in Zymosan: A Induced Multiorgan Failure

ABSTRACT

The pathogenesis of sepsis is not clearly understood. In animal models, the association of a high plasma TNF-alpha level with the frequent development of adult respiratory distress syndrome in septic conditions suggests that TNF-alpha plays a major role in the pathogenesis of the lung injury. Also, oxygen free radicals are known to participate in the pathogenesis of multiorgan failure. However, the relations between those factors have not been elucidated clearly. In pharmacological dosage, growth hormone (GH) promotes positive nitrogen balance and anabolic metabolism. There have been many studies about the therapeutic effects of GH in sepsis; However, the exact mechanism is not known. The purpose of this study is to evaluate the mechanism of the therapeutic action of GH in sepsis induced by intraperitoneal injection of Zymosan-A in an animal model. The experimental animals were female Sprague-Dawley rats which were devided into three groups a control group, a group injected intraperitoneally with Zymosan-A, and a group injected intraperitoneally with Zymosan-A and intramurally with growth hormone. After the lapse of time of 6, 12, 24, 48, and 72 hrs., the rats were sacrificed; then the histopathologic findings for the lung tissue were examined, and the levels of malondialdehyde(MDA) in the lung tissue and TNF-alpha in the blood were measured. In the Zymosan-A-injected group, an increment of infiltration by lymphocytes and neutrophils was observed, the MDA levels in the lung tissue were remarkably increased and reached a peak level 24 hrs. after Zymosan-A injection, and the TNF-alpha levels in the plasma were markedly increased. In the Zymosan-A-plus GH-injected group, there were less infiltration of inflammatory cells and less interstitial edema, and significantly suppressed increments of TNF-alpha and MDA. It can be concluded that GH inhibits the production of TNF-alpha and MDA in sepsis and protect against systemic tissue injury. However, the mechanism for the inhibition of the TNF-alpha production was not elucidated by this study. Further experiments are required.