Drynda Angelika, Obmińska-Mrukowicz Bożena, Mączyński Marcin, Ryng Stanisław
Faculty of Veterinary Medicine, Department of Biochemistry, Pharmacology and Toxicology, Wrocław University of Environmental and Life Sciences , Wrocław , Poland and.
Immunopharmacol Immunotoxicol. 2015 Apr;37(2):148-57. doi: 10.3109/08923973.2014.1000496. Epub 2015 Jan 9.
5-Amino-3-methyl-4-isoxazolecarboxylic acid hydrazide is a non-cytotoxic synthetic isoxazole derivative with considerable immunomodulatory properties demonstrated in in vitro experiments. The aim of this study was to investigate the influence of this compound, depending on the dosage and schedule of treatment, on lymphocyte subsets in non-immunized mice and humoral immune response in SRBC (sheep red blood cells)-immunized mice. An analysis of lymphocyte subsets was carried out by flow cytometry, using specific monoclonal antibodies stained with fluorescein isothiocyanate (FITC) or phycoerythrin (PE). In the SRBC-immunized mice, the influence of the compound on the humoral response was determined, depending on the time of administration relative to the antigen. The number of plaque forming cells (PFC) was determined by a local hemolysis technique in an agar gel. Total and 2-mercaptoethanol resistant serum agglutination titers were defined by active hemagglutination test carried out on microplates. The investigated hydrazide was able to modulate the percentage and absolute number of T lymphocyte subsets in the thymus, and T and B lymphocytes in the peripheral lymphatic organs. It also enhanced humoral immune response in SRBC-immunized mice by increasing the number of cells producing hemolytic anti-SRBC antibodies (PFC) and by augmenting the level of total and 2-mercaptoethanol resistant hemagglutinin. The present study showed modulatory effects of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide on lymphocyte subsets and humoral immune response in mice. This compound could be potentially useful for the treatment of autoimmune diseases, infections or as an adjuvant for boosting the efficacy of vaccines.
5-氨基-3-甲基-4-异恶唑甲酰肼是一种无细胞毒性的合成异恶唑衍生物,体外实验表明其具有显著的免疫调节特性。本研究旨在探究该化合物根据治疗剂量和疗程,对未免疫小鼠淋巴细胞亚群以及经绵羊红细胞(SRBC)免疫小鼠的体液免疫反应的影响。通过流式细胞术,使用异硫氰酸荧光素(FITC)或藻红蛋白(PE)标记的特异性单克隆抗体对淋巴细胞亚群进行分析。在经SRBC免疫的小鼠中,根据化合物相对于抗原的给药时间,确定其对体液反应的影响。通过琼脂凝胶中的局部溶血技术测定噬斑形成细胞(PFC)的数量。通过在微孔板上进行的活性血凝试验确定总血清凝集滴度和对2-巯基乙醇有抗性的血清凝集滴度。所研究的酰肼能够调节胸腺中T淋巴细胞亚群以及外周淋巴器官中T和B淋巴细胞的百分比和绝对数量。它还通过增加产生抗SRBC溶血抗体的细胞数量(PFC)以及提高总血清凝集素和对2-巯基乙醇有抗性的血凝素水平,增强了经SRBC免疫小鼠的体液免疫反应。本研究显示了5-氨基-3-甲基-4-异恶唑甲酰肼对小鼠淋巴细胞亚群和体液免疫反应的调节作用。该化合物可能对治疗自身免疫性疾病、感染或作为增强疫苗效力的佐剂具有潜在用途。