Effect of CI-949 and CI-959 on immune function and lymphoid organs in rats.

TitleEffect of CI-949 and CI-959 on immune function and lymphoid organs in rats.
Publication TypeJournal Article
Year of Publication1989
AuthorsKoller LD, Voller BE, Hedstrom OR, Steppan LG, Kerkvliet NI, Thueson DO
JournalInternational journal of immunopharmacology
Volume11
Issue5
Pagination509-16
Date Published1989
ISSN0192-0561
KeywordsAnimals, Antibody Formation, Azoles, Body Weight, Cytotoxicity Tests, Immunologic, Enzyme-Linked Immunosorbent Assay, Hypersensitivity, Hypersensitivity, Delayed, Immunity, Immunity, Cellular, Indoles, Killer Cells, Natural, Lymphocytes, Male, Rats, Rats, Inbred Strains, Spleen, Tetrazoles, Thiophenes, Thymus Gland
Abstract

The immunotoxic properties of two experimental antiallergic drugs, CI-949 and CI-959, were investigated. Wistar rats were gavaged once (CI-949) or twice (CI-959) daily for 21 days with the drugs. Immunotoxicity was assessed using the enzyme-linked immunoabsorbant assay (ELISA) for humoral immunity, a delayed-type hypersensitivity (DTH) procedure for cell-mediated immunity, and natural killer cell (NKC) activity to evaluate spontaneous cytotoxicity. Ratios of body weight to spleen, thymus, liver and kidney weights were determined. Routine histopathology was performed on lymphoid tissue and other body organs. Although 100 mg/kg/day of CI-949 had some stimulating effect on antibody production and NKC cytotoxicity, no consistent immunomodulation was apparent. Except for a significant increase in liver weight at the 100 mg/kg dose of CI-949, no other toxic effects were observed. In contrast to CI-949, CI-959 significantly (P less than 0.05) suppressed antibody production at the 100 mg/kg dose and impaired the DTH reaction, although not significantly. Natural killer cell cytotoxicity was unaffected by 100 mg/kg CI-959. Decreased body weight and histopathological lesions were observed in the thymus and spleen of rats administered 100 mg/kg CI-959. These lesions ranged from mild to severe lymphoid depletion which was also reflected in significantly (P less than 0.05) reduced spleen and thymus organ weight to body weight ratios. Since 100 mg/kg of CI-959 produced toxicological and pathological alterations in the exposed rats, these data suggest that CI-959 is not highly or specifically immunotoxic at dosages lower than those that alter conventional toxicological parameters used in new drug testing programs.(ABSTRACT TRUNCATED AT 250 WORDS)

Alternate JournalInt. J. Immunopharmacol.