IMMUNOTOXICITY OF SOLUBLE BETA-GLUCANS INDUCED BY INDOMETHACIN TREATMENT

(1-->3)-beta-D-Glucan (beta-glucan) is a biological response modifier that regulates host immune response. However, the side effects of this drug have not been extensively examined. In this study, we found that the combination of a beta-glucan and a nonsteroidal anti-inflammatory drug, indomethacin, induced lethal toxicity in mice. Lethal toxicity of orally administered indomethacin (multiple administration to ICR mi ce; once a day for 2 weeks) was 0/8 (2.5 mg kg(-1)) and 5/8 (5 mg kg(- 1)) (death/total) over 2 weeks. The toxicity was enhanced to 3/8 and 8 /8 in mice treated with a clinical beta-glucan preparation, sonifilan (250 mu g/mouse, single i.p. administration on day 0). A similar effec t was observed for other beta-glucans, including SSG, grifolan, zymosa n A and zymocel. Enhanced lethal toxicity resulted from a single p.o. administration of indomethacin on day 5 to day 9 after multiple beta-g lucans administration. Interferon-gamma, interleukin-6 and colony stim ulating factor concentrations in sera of indomethacin/beta-glucan-trea ted mice were significantly elevated. These results strongly suggest t hat indomethacin/beta-glucan treatment induces lethality in mice by ma ladjusting the cytokine network. (C) 1996 Federation of European Micro biological Societies. Published by Elsevier Science B.V. All rights re served.