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 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.
Monti
G
G
INSERM U131, Clamart, France.
Jaurand
M C
MC
Monnet
I
I
Chretien
P
P
Saint-Etienne
L
L
Zeng
L
L
Portier
A
A
Devillier
P
P
Galanaud
P
P
Bignon
J
J
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
D016827:CD8 Antigens; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D019798:Neopterin; D007371:Interferon-gamma