TREATMENT OF ENDOTOXEMIC MICE WITH ANTI-INTERLEUKIN-6 ANTIBODY PARADOXICALLY INCREASES INTERLEUKIN-6 LEVELS AND STIMULATES MUCOSAL PROTEIN-SYNTHESIS

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 wit h different doses of lipopolysaccharide (LPS) and protein synthesis wa s measured in jejunal mucosa at various time points up to 24 hours aft er injection of LPS, (2) mice were pretreated with anti-IL-6 antibody before injection of LPS; and (3) mice were injected with recombinant I L-6 and mucosal protein synthesis was measured 24 hours later. Results : Treatment of mice with LPS resulted in a dose- and time-dependent in crease in mucosal protein synthesis. Pretreatment of endotoxemic mice with anti-IL-6 antibody resulted in a paradoxical increase in plasma a nd tissue levels of IL-6 and a further increase in mucosal protein syn thesis. Administration of IL-6 to normal mice resulted in increased mu cosal protein synthesis. Conclusion: The increase in mucosal protein s ynthesis seen during endotoxemia may be regulated at least in part by IL-6.