MODULATION OF TUMORICIDAL FUNCTION IN ALVEOLAR MACROPHAGES FROM LUNG-CANCER PATIENTS BY INTERLEUKIN-6

Previous studies have demonstrated that alveolar macrophages from lung cancer patients are impaired in their ability to develop tumoricidal function when stimulated by activators such as interferon gamma + lipo polysaccharide. However, these same macrophages have been shown to dev elop significant tumoricidal function when precultured with macrophage -depleted allogeneic peripheral blood lymphocytes from normal donors, an effect that was lost by the elimination of natural killer cells fro m the allogeneic lymphocyte population. In the present study, the effe ct of each activation condition on the expression of mRNA for interleu kin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor alpha (TNF alpha) and IL-6 was determined using reverse transcription/polymerase chain reaction. The results show that the non-permissive activation co ndition is associated with the expression of mRNA for IL-6 while the p ermissive activation condition is not. Antibodies against IL-6 were su bsequently shown to permit the development of tumoricidal function in alveolar macrophages stimulated with interferon gamma + lipopolysaccha ride while IL-6 protein was shown to inhibit the stimulatory action of allogeneic lymphocytes on the development of tumoricidal function in the same alveolar macrophages. Neither the permissive (i.e. allogeneic lymphocyte stimulation) nor the non-permissive (i.e. interferon gamma + lipopolysaccharide) activation condition had any effect on the capa city of alveolar macrophages from lung cancer patients to express mRNA for IL-1 alpha, IL-1 beta or TNF alpha. These results show that IL-6 can regulate the ability of alveolar macrophages from lung cancer pati ents to be stimulated by interferon gamma + lipopolysaccharide to deve lop significant tumoricidal function. They also show that allogeneic l ymphocytes have the capacity to downregulate IL-6 mRNA synthesis by al veolar macrophages thereby permitting the development and/or expressio n of macrophage tumoricidal function.