Immunoregulatory effects of 4-(4-chlorophenyl)-1-(5-amino-3-methylisoxazole-4-carbonyl)-thiosemicarbazide (06K) in non-immunized and SRBC-immunized mice.

Abstract

Immunoregulatory properties of 06K derivative (4-(4-chlorophenyl)-1-(5-amino-3-methylisoxazole-4-carbonyl)-thiosemicarbazide) in mouse in vivo models were investigated. Several in vivo models were used: humoral and cellular immune response, carrageenan inflammatory reaction and determination of lymphocyte subsets in non-immunized mice. The compound administered before or after immunization with sheep erythrocytes (sheep red blood cell (SRBC)) elevated the number of plaque-forming cells (PFC), and this effect was stronger at lower doses. Although total haemagglutinin titres to SRBC decreased upon postimmunization treatment, IgG titre increased. In the model of delayed-type hypersensitivity (DTH) to ovalbumin (OVA), the compound, applied intraperitoneally before an eliciting dose of an antigen but not before immunization, inhibited the magnitude of a cutaneous reaction. Further, 06K significantly diminished carrageenan-induced foot pad inflammation when administered 1 h before carrageenan. The compound, administered intraperitoneally to naïve mice, elicited changes in weight, cell number in lymphoid organs and content of lymphocyte subsets, depending on the dose and number of applications. Phenotypic changes included increased turnover of thymocytes, changes in B-cell distribution in spleens and lymph nodes, increased percentage of CD8+ cells and regulatory CD4+ CD25+ Foxp3+ T cells. Immunoregulatory properties of 06K involve mobilization of lymphopoiesis and generation of regulatory T cells.