IL-12-induced production of IL-10 and interferon-gamma by mononuclear cells in lung cancer-associated malignant pleural effusions.
Interleukin (IL)-12 enhances natural killer (NK) activity and induces interferon gamma (IFN-gamma) production. Recently, it was shown that IL-12 induces IL-10 production by human T cells and NK cells, as a negative feedback for IL-12-induced immune responses. In the present study, in order to investigate the functions of host immune cells existing in contact with cancer cells, we examined the effect of IL-12 on the induction of non-major histocompatibility complex (MHC)-restricted killer activity and of IFN-gamma and IL-10 production by pleural and peripheral blood mononuclear cells (MNC), isolated from 40 lung cancer patients and 20 control subjects. IL-12 induced significant killer activity in pleural MNC from lung cancer patients, as well as those in peripheral blood, against a small cell lung cancer cell line (SBC-3). In lung cancer patients, pleural MNC incubated with IL-12 produced more IFN-gamma than blood MNC. In addition, when stimulated with both IL-12 and IL-2, pleural MNC produced more IL-10 than blood MNC. This is the first study reporting that MNC from pleural effusions of patients with lung cancer can produce both type 1 (IFN-gamma) and type 2 (IL-10) cytokines following exposure to IL-2 and IL-12. These observations suggest that control of IL-10 production at the microenvironment level may be important for the efficacy of human lung cancer immunotherapy with IL-12.
Takeuchi
Eiji
E
Third Department of Internal Medicine, The University of Tokushima School of Medicine, Kuramoto-cho 3, Tokushima 770-8503, Japan.
Yanagawa
Hiroaki
H
Suzuki
Yoshihiro
Y
Shinkawa
Kunihiro
K
Ohmoto
Yasukazu
Y
Bando
Hiroyasu
H
Sone
Saburo
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D018288:Carcinoma, Small Cell / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008175:Lung Neoplasms / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma