title: Modulation of tumoricidal function in alveolar macrophages from lung cancer patients by interleukin-6.
abstract: 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 + lipopolysaccharide. However, these same macrophages have been shown to develop 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 from the allogeneic lymphocyte population. In the present study, the effect of each activation condition on the expression of mRNA for interleukin-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 condition is associated with the expression of mRNA for IL-6 while the permissive activation condition is not. Antibodies against IL-6 were subsequently shown to permit the development of tumoricidal function in alveolar macrophages stimulated with interferon gamma + lipopolysaccharide 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 capacity 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 patients to be stimulated by interferon gamma + lipopolysaccharide to develop significant tumoricidal function. They also show that allogeneic lymphocytes have the capacity to down-regulate IL-6 mRNA synthesis by alveolar macrophages thereby permitting the development and/or expression of macrophage tumoricidal function.
authors.affiliation: Section of Medical Oncology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Ahn
authors.forename: K P
authors.initials: KP
authors.lastname: Siziopikou
authors.forename: J M
authors.initials: JM
authors.lastname: Plate
authors.forename: L
authors.initials: L
authors.lastname: Casey
authors.forename: M
authors.initials: M
authors.lastname: Silver
authors.forename: J E
authors.initials: JE
authors.lastname: Harris
authors.forename: D P
authors.initials: DP
authors.lastname: Braun
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008175:Lung Neoplasms / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000906:Antibodies; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007371:Interferon-gamma