Regulation of IL-6 and the hepatic IL-6 receptor in acute inflammation in vivo

The serum levels of interleukin 6 (IL-6) and the expression (mRNA) of the 80 kDa IL-6 receptor (IL-6R) were examined in three different models of acute inflammation. Rats were treated with either Freund's complete adjuvant (FA) via intraperitoneal injection, LPS via intravenous injection, or turpentine via subcutaneous injection. Using bio- and specific immunoassays, rat serum levels of IL-6, corticosterone, and acute phase proteins were quantified. LPS treatment induced the quickest and greatest serum IL-6 response (> 100 ng/ml within 3 h). In comparison, sera from turpentine and FA-treated rats contained much lower levels of IL-6 activity (< 10 ng/ml). Serum corticosterone levels increased by 3 h after injection in all three models, and equivalent raised serum levels of acute phase proteins were detected within 12-24 h. The expression of IL-6 receptor mRNA in hepatocytes increased markedly as early as 3 h after treatment and message levels began to decline by 6-12 h in all three models. To analyze the individual effects of raised corticosterone and IL-6 on the expression of hepatic IL-6R mRNA, rats were injected with either dexamethasone (Dex) or purified recombinant rat IL-6 (rIL-6) via intraperitoneal injection. Rats injected with rIL-6 showed highly induced IL-6R mRNA levels as early as 1 h after injection, and Dex-injected rats showed a significant but less dramatic rise in IL-6R message levels. Dex- or rIL-6-injected rats demonstrated a distinct profile of acute phase protein response different from that seen in the three experimental models. Regulation of IL-6R gene expression in the liver in vivo depends on a complex interaction between the hepatocyte and a combination of cytokines and other hormones.