INTERLEUKIN-6 DELAYS NEUTROPHIL APOPTOSIS

Background: Neutrophil (PMN) apoptosis promotes the phagocytosis of PM Ns without inciting an inflammatory response or local cytotoxic effect . This is important in the normal resolution of inflammatory processes and the control of tissue injury. Conversely, a delay in PMN apoptosi s may facilitate PMN-mediated organ dysfunction by extending PMN funct ional integrity at an inflammatory site. Elevated circulating and tiss ue levels of interleukin-6 (IL-6) have been associated with postinjury organ dysfunction, and IL-6 appears to augment PMN cytotoxic function s. Therefore, we hypothesized that IL-6 delays PMN apoptosis, thereby enhancing PMN-mediated cytotoxicity. Methods: Neutrophils isolated fro m healthy human donors were incubated for 24 hours in enriched RPMI 16 40 cell culture medium at 37 degrees C in 5% carbon dioxide. Subgroups were incubated With IL-6, heat-denatured IL-6, or buffer alone. Apopt osis was assessed morphologically using acridine orange-ethidium bromi de stain, and biochemically by DNA gel electrophoresis. Functional cap acity of PMNs was assessed by superoxide generation after activation w ith phorbol myristate acetate or platelet-activating factor plus formy lmethionyl-leucyl-phenylalanine. Results: Treatment with IL-6 resulted in a greater population of surviving (nonapoptotic) PMNs after 24 hou rs. In addition, the IL-6-treated population produced more superoxide after 24 hours than did the untreated or heat-denatured IL-6-treated g roups, after either activating stimulus. Conclusions: Interleukin-6 de lays PMN apoptosis, resulting in a larger population of surviving PMNs with a greater collective capacity for superoxide production. This co uld potentially facilitate PMN-mediated tissue injury and may be a mec hanism whereby IL-6 contributes to organ dysfunction.