INTERLEUKIN-6 STIMULATES HEPATIC TRIGLYCERIDE SECRETION IN RATS

Interleukin-6 (IL-6) not only regulates a variety of immune functions, but also is the most potent cytokine in inducing the hepatic acute ph ase proteins. We determined the effect of IL-6 on serum lipid levels a nd the mechanism of IL-6-induced hypertriglyceridemia in rats. Intrave nous administration of IL-6 (0.1-10 mu g/200 g BW) increased serum tri glyceride levels in a dose-dependent manner. One hour after IL-6 admin istration, serum triglyceride levels were increased, with peak values at 2 h (2.2-fold increase). Serum cholesterol levels also increased, b ut the effect was delayed, first occurring at 4 h and peaking at 8 h ( 1.24-fold increase). IL-6 treatment increased hepatic triglyceride sec retion without decreasing the clearance of triglyceride-rich lipoprote ins, indicating that the hypertriglyceridemia was due to increased sec retion by the liver. Furthermore, IL-6 stimulates lipolysis, and the i ncreased delivery of FFA to the liver significantly contributed to the IL-6-induced hypertriglyceridemia. Neither alpha(1)- nor beta-adrener gic receptor antagonists affected the hypertriglyceridemia induced by IL-6, whereas previous studies have shown that endotoxin-induced hyper triglyceridemia was blocked by alpha-adrenergic receptor antagonists. These results demonstrate that IL-6 induces hypertriglyceridemia by st imulating hepatic triglyceride secretion independent of endogenous cat echolamines. Thus, changes in hepatic triglyceride metabolism are anot her acute phase response that can be induced by IL-6.