The metabolic effects of endotoxin are differentially affected by the pattern of GH administration in the rat

GH treatment can increase the mortality and morbidity of critically ill pat ients. The mechanisms of these harmful effects of GH are unknown but have b een. in part., ascribed to interactions between GH and the immune system. B ecause GH has pattern-dependent actions we have now compared the dose-relat ed effects of continuous and intermittent GH treatment given with or withou t an endotoxin (lipopolysaccharide; LPS) challenge. Male Wistar rats (n=6 p er group) were treated for 5 days with recombinant human GH (0, 10, 100 or 1000 mug/kg per day) using either continuous s.c. infusion by osmotic minip ump or intermittent twice daily s.c. injections. On day 4, endotoxin (5 mg/ kg, i.p.) was injected and the animals monitored for a further 16 h. LPS ad ministration alone led to neutrophilia and lymphopoenia, with increased pla sma concentrations of urea, cholesterol, triglyceride, insulin and leptin, and decreased levels of IGF-I. High dose GH infusion (1000 mug/kg per day) followed by LPS caused greater increases in plasma urea, cholesterol, trigl yceride, sodium and magnesium, but lower plasma glucose and insulin levels, than treatment with LPS alone. In contrast, twice daily injections of GH d id not enhance these effects of endotoxin. In conclusion, the effects of en dotoxin on plasma electrolytes. lipids, urea, glucose and insulin are diffe rentially affected by the pattern of GH administration in the rat.