Zimecki Michał, Artym Jolanta, Ryng Stanisław, Obmińska-Mrukowicz Bozena
Laboratory of Immunobiology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, PL 53-114 Wrocław, Poland.
Pharmacol Rep. 2008 Mar-Apr;60(2):183-9.
The aim of this study was to evaluate efficacy of an isoxazole derivative RM11 to accelerate reconstitution of selected immune activities in cyclophosphamide (CP)-immunocompromised mice. We demonstrated that administration of fifteen 10 mug intraperitoneal doses of RM11, following a sublethal (200 mug/kg) dose of CP, significantly stimulated the number of antibody-forming cells (AFC) to sheep erythrocytes (SRBC) as determined 35 days after the CP treatment. Similarly, treatment of the CP-injected mice with 7 doses of RM11 significantly enhanced generation of delayed type hypersensitivity (DTH) to ovalbumin (OVA). Moreover, in that model, the treatment of mice with RM11 accelerated the process of myelopoiesis. RM11 also counteracted the suppressive action of methotrexate (MTX) in the in vitro model of the humoral immune response to SRBC. The phenotypic studies with fluorocytometer revealed that intraperitoneal 10 mug dose of RM11 significantly elevated the percentage of mature (CD3(+), CD4(+) and CD8(+)) T cells in the spleen and down-regulated the content of CD19(+) cells. We conclude that RM11 may be of potential therapeutic value in restoration of the immune status in patients undergoing chemotherapy.
本研究的目的是评估异恶唑衍生物RM11在环磷酰胺（CP）免疫受损小鼠中加速特定免疫活性重建的疗效。我们证明，在亚致死剂量（200μg/kg）的CP之后，腹腔注射15次10μg剂量的RM11，显著刺激了CP治疗35天后测定的针对绵羊红细胞（SRBC）的抗体形成细胞（AFC）数量。同样，用7剂RM11治疗注射CP的小鼠，显著增强了对卵清蛋白（OVA）的迟发型超敏反应（DTH）的产生。此外，在该模型中，用RM11治疗小鼠加速了骨髓生成过程。RM11还在针对SRBC的体液免疫反应的体外模型中抵消了甲氨蝶呤（MTX）的抑制作用。用荧光细胞仪进行的表型研究表明，腹腔注射10μg剂量的RM11显著提高了脾脏中成熟（CD3(+)、CD4(+)和CD8(+)）T细胞的百分比，并下调了CD19(+)细胞的含量。我们得出结论，RM11在恢复接受化疗患者的免疫状态方面可能具有潜在的治疗价值。
