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Immunorestoring activity of isoxazole derivative R-13

Michał Zimecki 1Jolanta Artym 1Maja Kocięba 1Bożena Obmińska-Mrukowicz 2Marcin Mączyński 3Stanisław Ryng 3

1. Polish Academy of Sciences, Institute of Immunology and Experimental Therapy (IITD), Rudolfa Weigla 12, Wrocław 53-114, Poland
2. University of Environmental and Life Sciences, Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Norwida 25/27, Wrocław 50-375, Poland
3. Wroclaw Medical University, Faculty of Pharmacy, Department of Organic Chemistry, Borowska 211A, Wrocław 50-556, Poland

Abstract

Immunoreconstituting effects of R-13 compound (3,5-dimethylisoxazole[5,4-e]6H-triazepin-4-one) on immune status of mice treated with cyclophosphamide (CP) were evaluated. In this study we evaluated  effects of R-13 administration on: phenotypic changes of cells in lymphoid organs in normal mice, leukocyte and splenocyte numbers and blood cell composition in CP-treated mice, spontaneous and mitogen-induced splenocyte proliferation as well as humoral and cellular immune responses. In normal mice R-13 significantly elevated percentages of CD3+ and CD4+ cells in the spleens and lymph nodes, accompanied by reduction of CD19+ cells. In CP-treated mice, R-13, administered in five doses, increased number of blood leukocytes and splenocytes, spontaneous and Con A-induced splenocyte proliferation (day 15 after CP). Blood picture analysis showed decreases of neutrophil and eosinophil levels and appearance of lymphocyte immature forms. The number of circulating lymphocytes increased by 2-fold whereas absolute numbers of neutrophils remained unchanged. The cellular response to OVA (day 15 following CP) was completely restored using five R-13 doses. The humoral immune response, determined 38 days after CP administration, was also significantly restored by using ten R-13 doses. In conclusion, we presented characteristics of isoxazole derivatives R-13 which exhibits selective T-cell-tropic activity and accelerates restoration of the cellular and humoral immune responses. Such a property and other features such as lack of toxicity and bioaccessibility at oral administration are desirable for use in immunocompromised patients. It is also conceivable that R-13 could find application in states of T-cell deficiencies. This study was supported by a statuary grant from the Polish Ministry of Education, No 4/2009, for the Institute of Immunology, Polish Academy of Sciences, Wrocław, Poland, and by the State Committee for Scientific Research, grant No. KBN 3PO5F 01224.

 

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Submitted: 2014-03-25 22:55
Revised:   2014-05-02 18:55