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.