Immunomodulatory activity of the newly synthesized compound TOK-8801 (N-(2-phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo(2,1-b)thiazole-2-carboxamide).

Abstract

Abstract-The in vitro and in vivo effects of the newly synthesized compound 6,thiazole 2-carboxamide) on immune responses were investigated in comparison with that of levamisole (LMS). TOK-8801 enhanced the anti-sheep red blood cells (SRBC) plaque forming cells (PFC) response and mitogen-induced proliferative responses in murine splenocytes and thymocytes in vitro at concentrations of 10-7-10-5 M, while LMS augmented these responses at 10-4M. The stimulatory effect of TOK-8801 as well as LMS on the antibody production was eliminated by the removal of T cells. TOK-8801 (0.5 mg/kg, p.o.) suppressed the in vivo generation of anti-SRBC PFC in normal mice, but the compound restored the depressed antibody production in restraint-stress mice which was mainly caused by helper T cell defects. From these results, TOK-8801 was shown to have an immunomodulatory activity in the an tibody production.

Induction of prolonged elevation of interleukin 2 in the culture medium of murine splenocytes by their precultivation before mitogenic stimulations and its potentiation by glucocorticoid treatment and restraint stress loading.

“…Restraint stress loading: Stress loading was conducted as described by Fujiwara et al (16). BALB/c mice were fixed in restraint cages for 12 hr per day during daytime hours (8:00-20:00) and placed in home cages for the remaining 12 hr with food and water ad libitum.…”