Immunomodulatory activity of Wy-18,251 (3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid).

Abstract

The in vitro and in vivo effects of the experimental immunomodulatory agent Wy-18,251 (3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid) were studied in comparison with levamisole and indomethacin. Levamisole (4 mg/kg, i.v.) but not Wy-18,251 (less than or equal to 10 mg/kg, i.v.) enhanced carbon clearance rates in vivo in mice. Both Wy-18,251 and levamisole (100 mg/kg, p.o.) significantly suppressed the symptoms of experimental allergic encephalomyelitis (EAE) in rats injected with spinal cord emulsion, but neither were as effective as tilorone in this model. Wy-18,251 and levamisole (1-100 mg/kg, p.o.) suppressed the in vivo generation of plaque-forming cells (PFC) in mice immunized with sheep red blood cells while indomethacin (9 mg/kg, p.o.) enhanced PFC formation. All 3 agents (10(-5) - 10(-6) M) enhanced the in vitro ovalbumin (OA)-specific and Con A- or PHA-induced proliferative response and Con A-stimulated interleukin 2 (IL-2) synthesis of rat spleen cells. Furthermore, in vivo treatment of rats with 1-10 mg/kg (p.o.) of Wy-18,251 and levamisole but not indomethacin increased the subsequent in vitro mitogen or antigen (OA) responsiveness of spleen cells. None of the drugs (10(-5) - 10(-7) M) influenced the natural killer cell (NK) activity of rat spleen cells when incorporated directly into the 51Cr release NK assay.