Chloramphenicol and the inflammatory response in the rat. Upregulation of the gene for T₂-kininogen in liver

Recent observations have indicated that cytokine and glucocorticoid mediators of the inflammatory response in mammals interfere with the mitochondrial respiratory capacity of cultured cells. Here, we report studies on the effect of the antibiotic chloramphenicol (CAP), a potent mitochondrial protein synthesis and respiratory inhibitor, on the inflammatory response in the rat. CAP was injected daily (i.p.) at doses of 30, 100 and 300 mg kg^-1 during a period of 10 days. Acute inflammation was induced on day 10 by s.c. injection of carrageenan into the hindpaws. Paw edema reaction and liver and serum expression of the acute phase protein T-kininogen were used as markers of the local and systemic inflammatory response, respectively. Albumin was selected as a liver protein whose expression is little or not affected in inflamed rats. We found that the swelling process induced locally by carrageenan injection was significantly altered in rats treated with CAP at the dose level of 300 mg kg^-1. The inhibitory effect of CAP was transient, extending up to 3 hr after carrageenan injection. CAP was observed also to alter the mitochondrial respiratory capacity of liver cells, reducing cytochrome C oxidase activity up to 50%. In contrast, liver immunoreactive T- kininogen content and the T₂-kininogen mRNA steady-state level were found to increase in a dose-related manner in CAP-treated animals. These values were slightly different from those recorded in control rats inflamed with carrageenan. No significant increase of T-kininogen serum content was seen at all dose levels of CAP injected. Among inflamed animals, those exposed long- term to CAP had elevated liver and serum T-kininogen content and T₂- kininogen mRNA steady-state levels. Expression of the gene for albumin was not affected in rats treated or not with CAP. The present observations indicate that CAP influences both local and systemic inflammatory responses in the rat.