Treatment of endotoxemic mice with anti-interleukin-6 antibody paradoxically increases interleukin-6 levels and stimulates mucosal protein synthesis

Q. Wang, J. E. Fischer and P. O. Hasselgren
Department of Surgery, University of Cincinnati, Ohio, USA.

OBJECTIVE: To test the role of interleukin-6 (IL-6) in the regulation of mucosal protein synthesis during endotoxemia. EXPERIMENTAL DESIGN: Three series of experiments were performed: (1) mice were injected with different doses of lipopolysaccharide (LPS) and protein synthesis was measured in jejunal mucosa at various time points up to 24 hours after injection of LPS; (2) mice were pretreated with anti-IL-6 antibody before injection of LPS; and (3) mice were injected with recombinant IL-6 and mucosal protein synthesis was measured 24 hours later. RESULTS: Treatment of mice with LPS resulted in a dose- and time-dependent increase in mucosal protein synthesis. Pretreatment of endotoxemic mice with anti-IL-6 antibody resulted in a paradoxical increase in plasma and tissue levels of IL-6 and a further increase in mucosal protein synthesis. Administration of IL-6 to normal mice resulted in increased mucosal protein synthesis. CONCLUSION: The increase in mucosal protein synthesis seen during endotoxemia may be regulated at least in part by IL-6.