Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 68, Issue 12, Pages 1613-1620Publisher
WILEY-BLACKWELL
DOI: 10.1111/jphp.12631
Keywords
cellular immune response; humoral; isoxazoles; mice; suppression
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Funding
- Wroclaw University of Environmental and Life Sciences [B030/0027/15]
- European Union as a part of the European Social Found from Marshal Office of Lower Silesia [DG-G/3357/14]
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ObjectivesImmunoregulatory properties of 06K derivative (4-(4-chlorophenyl)-1-(5-amino-3-methylisoxazole-4-carbonyl)-thiosemicarbazide) in mouse in vivo models were investigated. MethodsSeveral in vivo models were used: humoral and cellular immune response, carrageenan inflammatory reaction and determination of lymphocyte subsets in non-immunized mice. Key findingsThe 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 naive 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. ConclusionsImmunoregulatory properties of 06K involve mobilization of lymphopoiesis and generation of regulatory T cells.
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