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)