Suppression of cell-mediated immune responses in vivo and in vitro by 1-thiocarbamoyl-2-imidazolidinone

Abstract

Both in vivo and in vitro, the niridazole metabolite, 1-thiocarbamoyl-2-imidazolidinone (TCI), was found to suppress various manifestations of cell-mediated immunity. In vivo, doses of 10(-6) g/kg every other day delayed rejection of BALB/cJ (H--2d) skin allografts by C57BL/6J (H--2b) mice. Much lower single doses (approximately 10(-11) g/kg) markedly reduced both pulmonary granuloma formation around. Schistosoma mansoni eggs in C57BL/bJ mice and delayed footpad swelling in sensitized CF1 mice responding to S. mansoni egg antigen (SEA). Reduction of footpad swelling occurred when TCI was given 24 h before, but not 4 hr after, antigenic challenge. In vitro. SEA-dependent production of eosinophil stimulation promoter (ESP) activity by sensitized mouse spleen cells was decreased greater than 90% by 10(-10)g TCI/ml. TCI failed, however, to inhibit the action of preformed ESP lymphokine on eosinophils. The blastogenic response of sensitized lymph node cells to SEA was reduced by greater than 70% by 10(-11) to -10 (-8)g TCI/ml. The drug produced no effect on either antigen-dependent lymphokine production or blastogenesis if it was added 5 min after, instead of before, stimulating antigen.