INTRAPLEURAL PRODUCTION OF INTERLEUKIN-6 DURING MESOTHELIOMA AND ITS MODULATION BY GAMMA-INTERFERON TREATMENT

In vivo production of monokines was analyzed in 17 human malignant ple ural mesotheliomas. High concentrations of interleukin 6 (IL-6) were d etected in pleural effusions, contrasting with low levels of IL-1 beta and tumor necrosis factor alpha. This production arose from malignant cells, as shown by immunochemical analysis of pleural cells and by pr oduction of IL-6 by mesothelial cell lines. Intrapleural administratio n of recombinant human gamma-interferon to six patients led to a marke d decrease in intrapleural IL-6 concentrations in all cases. This trea tment was associated with in situ activation of macrophages and cytoto xic T-lymphocytes, as indicated by increased intrapleural neopterin an d soluble CD8 concentrations. In vitro gamma-interferon had no effect on the production of IL-6 by mesothelial cell lines but decreased the growth of 3 of 6 mesothelioma cell lines. These results indicate that systemic manifestations of malignant mesothelioma, including fever, ca chexia, and thrombocytosis may be related to the production of IL-6 by malignant cells, and that local gamma-interferon infusion may reduce this production by stimulating antitumoral immunity and/or by directly decreasing the proliferation of malignant cells.