title: Intrapleural production of interleukin 6 during mesothelioma and its modulation by gamma-interferon treatment.
abstract: In vivo production of monokines was analyzed in 17 human malignant pleural mesotheliomas. High concentrations of interleukin 6 (IL-6) were detected 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 production of IL-6 by mesothelial cell lines. Intrapleural administration of recombinant human gamma-interferon to six patients led to a marked decrease in intrapleural IL-6 concentrations in all cases. This treatment was associated with in situ activation of macrophages and cytotoxic T-lymphocytes, as indicated by increased intrapleural neopterin and 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, cachexia, 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.
authors.affiliation: INSERM U131, Clamart, France.
authors.forename: G
authors.initials: G
authors.lastname: Monti
authors.forename: M C
authors.initials: MC
authors.lastname: Jaurand
authors.forename: I
authors.initials: I
authors.lastname: Monnet
authors.forename: P
authors.initials: P
authors.lastname: Chretien
authors.forename: L
authors.initials: L
authors.lastname: Saint-Etienne
authors.forename: L
authors.initials: L
authors.lastname: Zeng
authors.forename: A
authors.initials: A
authors.lastname: Portier
authors.forename: P
authors.initials: P
authors.lastname: Devillier
authors.forename: P
authors.initials: P
authors.lastname: Galanaud
authors.forename: J
authors.initials: J
authors.lastname: Bignon
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis*; D008654:Mesothelioma / Q000378:metabolism* / Q000628:therapy; D019798:Neopterin; D010996:Pleural Effusion / Q000378:metabolism* / Q000628:therapy; D010997:Pleural Neoplasms / Q000378:metabolism* / Q000628:therapy; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D019798:Neopterin; D007371:Interferon-gamma