Exogenous interleukin 2 regulates interleukin 6 and nitric oxide but not interferon gamma and tumor necrosis factor alpha production in bronchoalveolar leukocytes from patients with small cell lung cancer.
The relationship and in situ interactions between interleukin 2 (IL-2)-regulated mediators remain unclear, particularly in lung cancer model. The purpose of the present study was to determine in vitro effect of IL-2 on the secretory activity of bronchoalveolar leukocytes from 11 patients with previously untreated small cell lung cancer (SCLC) and 9 patients with non-small cell lung cancer (NSCLC). Control group (n = 6) comprised patients who underwent diagnostic investigations and were free of any clinical or radiographic evidence of lung diseases. IL-2-induced secretion of mediators was compared with that following stimulation with lipopolisaccharide (LPS; 5 micrograms/ml) or Newcastle disease virus (NDV; 640 HU/ml). Obtained from bronchoalveolar lavages (BAL) cells were cultured for 24-48 h in the presence or absence of inducers. The levels of cytokines were determined in BAL cell supernatants by bioassays. Nitric oxide (NO) was estimated by colorimetric method in Griess reaction. Compared with normal controls, the spontaneous secretion of the above mediators excluding IFN-gamma in BAL cultures from NSCLC group was elevated by up to 20-30-fold and further increase was observed after stimulation with LPS. However, very low secretion of cytokines and NO was found in BAL leukocyte cultures activated by IL-2. In contrast, the cells obtained from SCLC group produced little detectable levels of TNF-alpha (median 12.0, range 3-45 U/ml), IFN-gamma (median 3, range 3-12 U/ml) and IL-6 (median 15, range 6-45 U/ml) in response to LPS and interferons, mainly IFN-alpha; (median 3, range 3-12 U/ml) in response to NDV. Although, upon IL-2-stimulation was observed only noteworthy production of IL-6 (median 405, range 45-1215 U/ml). IL-2-induced secretion of IL-6 was accompanied by up to 5-fold augmented secretion of NO in comparison with NSCLC group and healthy controls. These observations suggest that BAL cells from patients with lung cancers express a selective secretory activity and that IL-2 is an important regulatory factor of secondary production of IL-6 and NO. Utilization of IL-2 in therapeutic strategy in SCLC can lead to alterations in synthesis/release of biologically active IL-6 and NO that may contribute to the clinical settings.
Cembrzyńska-Nowak
M
M
Laboratory of Virology, Polish Academy of Sciences, Weigla, Wrocław, Poland.
Bieńkowska
M
M
Szklarz
E
E
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma