title: Modulation of cytokine production by a selenoorganic compound (AE-22) in hyperreactive or hyporeactive bronchoalveolar leukocytes of asthmatics or lung cancer patients.
abstract: We have found that many synthetic selenoorganic compounds, including ebselen, have immunotropic activity. These studies were designed to assess the effect of the analog of ebselen bis[2-pyridyl (2-carbamoyl) phenyl]diselenide (AE-22) on human leukocytes that may express various activation states. The cells were obtained from bronchoalveolar lavage (BAL) cells of patients with various inflammatory lung diseases. The AE-22-treated BAL cells from patients with bronchial asthma (n = 6) and with small cell lung cancer (SCLC) (n = 6) were compared with these in the peripheral blood leukocytes (PBL) from the same donors. The control group comprised 5 patients who underwent diagnostic examination and were free of any cancer or concomitant diseases. Secretion of TNF-alpha, IL-6, and IFN-gamma was considered as a marker of BAL or PBL cell activation. Different response of the cells and various effects of AE-22 were observed in relation to the origin and functional state of leukocytes. It was established that AE-22 can induce TNF-alpha, IL-6, and IFN-gamma in a dose-dependent manner in BAL cells and PBL isolated from healthy individuals. However, BAL cells were found to be less reactive than PBL as cytokine producers. In contrast, AE-22 had no effect on BAL cells obtained from patients with lung cancer, which were found to be hyporeactive to phytohemagglutinin and bacterial lipopolysaccharide and did not produce TNF-alpha, IL-6, or IFN spontaneously. The spontaneous release of cytokines by BAL cells from bronchial asthma patients, but not by PBL from the same individuals, was significantly (p < 0.01) higher than that from the cultures of healthy control subjects. The high secretion of cytokines by the locally activated BAL cells was significantly (p < 0.01) reduced after administration of AE-22. The results suggest that AE-22 has immunomodulatory activity. AE-22 can downregulate the hyporeactive BAL cells from asthmatics, but it appears to be inactive in BAL cells of cancer patients who can tolerate the cytokine inducers.
authors.affiliation: Laboratory of Virology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw.
authors.forename: M
authors.initials: M
authors.lastname: Cembrzyńska-Nowak
authors.forename: E
authors.initials: E
authors.lastname: Szklarz
authors.forename: A D
authors.initials: AD
authors.lastname: Inglot
mesh_terms: D000328:Adult; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001549:Benzamides / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016566:Organoselenium Compounds / Q000494:pharmacology*; D012016:Reference Values
chemical_list: D001549:Benzamides; D016207:Cytokines; D016566:Organoselenium Compounds; C110079:bis(2-pyridyl(2-cabamoyl)phenyl)diselenide