Role of interleukin 6 and transforming growth factor-beta in the induction of depressed splenocyte responses following sepsis

A. Ayala, J. B. Knotts, W. Ertel, M. M. Perrin, M. H. Morrison and I. H. Chaudry
Department of Surgery, Michigan State University, East Lansing 48824.

We examined whether (1) there is an association between elevated circulating levels of transforming growth factor-beta (TGF-beta) and splenocyte dysfunction during sepsis, and (2) administration of monoclonal antibodies to interleukin 6 (an inducer of TGF-beta release) or TGF-beta could ablate these changes. Blood and splenocytes were obtained from C3H/HeN mice at 1, 4, or 24 hours following cecal ligation and puncture or sham operation. Only at 24 hours after cecal ligation and puncture was there an association between elevated blood TGF-beta value and depressed splenocyte interleukin 2 release. Administration of monoclonal antibodies against interleukin 6, but not against TGF-beta (intraperitoneally immediately following cecal ligation and puncture), significantly decreased the blood levels of TGF-beta at 24 hours following cecal ligation and puncture and improved splenocyte interleukin 2 release. Thus, the judicious use of monoclonal antibodies against interleukin 6 may block the subsequent elevation of TGF-beta, thereby attenuating host immunosuppression during sepsis.

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