Immunotoxicity of soluble β-glucans induced by indomethacin treatment

• Published in: FEMS immunology and medical microbiology 1998-07, Vol.21 (3), p.171-179
• Main Authors: Yoshioka, Shoichi, Ohno, Naohito, Miura, Toshihide, Adachi, Yoshiyuki, Yadomae, Toshiro
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - toxicity; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - toxicity; beta-Glucans; Biological and medical sciences; Colony-Stimulating Factors - blood; Cytokines - blood; Dose-Response Relationship, Drug; Drug Synergism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glucans - administration & dosage; Glucans - toxicity; Immunobiology; Indomethacin; Indomethacin - administration & dosage; Indomethacin - toxicity; Interferon-gamma - blood; Interleukin-6 - blood; Lethal toxicity; Male; Mice; Mice, Inbred ICR; Modulation of the immune response (stimulation, suppression); Sizofiran - administration & dosage; Sizofiran - toxicity; Splenomegaly - chemically induced; Systemic inflammatory response syndrome; β-Glucan
• ISSN: 0928-8244; 1574-695X
• DOI: 10.1016/S0928-8244(98)00046-7

(1→3)-β- d-Glucan (β-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 β-glucan and a nonsteroidal anti-inflammatory drug, indomethacin, induced lethal toxicity in mice. Lethal toxicity of orally administered indomethacin (multiple administration to ICR mice; 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 β-glucan preparation, sonifilan (250 μg/mouse, single i.p. administration on day 0). A similar effect was observed for other β-glucans, including SSG, grifolan, zymosan A and zymocel. Enhanced lethal toxicity resulted from a single p.o. administration of indomethacin on day 5 to day 9 after multiple β-glucans administration. Interferon-γ, interleukin-6 and colony stimulating factor concentrations in sera of indomethacin/β-glucan-treated mice were significantly elevated. These results strongly suggest that indomethacin/β-glucan treatment induces lethality in mice by maladjusting the cytokine network.