Oral treatment with trimethoprim-sulfamethoxazole and zidovudine suppresses murine accessory cell-dependent immune responses.
Oral treatment with trimethoprim-sulfamethoxazole and zidovudine suppresses murine accessory cell-dependent immune responses.
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口服甲氧苄氨嘧啶-磺胺甲恶唑和齐多夫定可抑制小鼠辅助细胞依赖性免疫反应。
DOI：
10.1093/toxsci/55.2.335
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Mohagheghpour,N
中科院分区：
文献类型：
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作者：
Freund,YR;Dousman,L;MacGregor,JT;Mohagheghpour,N
甲氧苄啶-磺胺甲恶唑（TMP-SMX）常用于预防AIDS患者的卡氏肺孢子虫（PCP），但其治疗限制性反应的发生率较高。我们研究了口服TMP-SMX单独或与抗逆转录病毒药物齐多夫定（ZDV）联合给药对BALB/c小鼠造血和细胞免疫的影响。TMP-SMX（160：800 mg/kg）每日给药28天，对脾T淋巴细胞对同种异体肿瘤细胞（EL-4）或刀豆球蛋白A（ConA）的体外增殖反应以及脾B细胞对脂多糖（LPS）的体外增殖反应均无影响。240 mg/kg/天ZDV无免疫抑制作用，但引起轻度大红细胞贫血。联合治疗产生严重的全血细胞减少，脾细胞结构显著下降，脾巨噬细胞百分比下降61%。TMP-SMX + ZDV组脾脏CD 3+淋巴细胞百分比增加150%，但T细胞亚群比例和B细胞频率无变化。联合药物治疗不损害B细胞对LPS的增殖反应或T细胞对EL-4细胞的增殖反应。与巨噬细胞百分比的减少一致，T淋巴细胞对ConA的增殖反应显著降低。最佳ConA诱导的T细胞增殖需要辅助细胞（AC）的参与（例如，巨噬细胞）; EL-4细胞能够起到AC的作用。这些数据表明，ZDV与TMP-SMX协同作用，导致严重的血液毒性和抑制AC依赖性免疫功能，并表明这种治疗方案可能有助于艾滋病患者的免疫恶化。
Trimethoprim-sulfamethoxazole (TMP-SMX), commonly used for prophylaxis ofPneumocystis cariniipneumonia (PCP) in AIDS patients, often produces a high incidence of treatment-limiting reactions. We investigated the effect of oral administration of TMP-SMX alone or in combination with the antiretroviral drug zidovudine (ZDV) on hematopoiesis and cellular immunity in BALB/c mice. Daily treatment for 28 days with TMP-SMX (160:800 mg/kg) had no effect on hematopoiesis or theex vivoproliferative response of splenic T lymphocytes to allogeneic tumor cells (EL-4) or to concanavalin A (ConA), or that of splenic B cells to lipopolysaccharide (LPS). ZDV at 240 mg/kg/day was not immunosuppressive but caused a mild macrocytic anemia. Combined treatment produced severe pancytopenia, a significant drop in splenic cellularity, and a 61% decrease in the percentage of splenic macrophages. The percentage of splenic CD3+ lymphocytes increased 150% in the TMP-SMX + ZDV group, but the ratios of T-cell subsets and the frequency of B cells remained unchanged. Combined drug treatment did not impair the proliferative response of B cells to LPS or that of T cells to EL-4 cells. In concert with the reduction in the percentage of macrophages, the proliferative response of T lymphocytes to ConA decreased significantly. Optimal ConA-induced T-cell proliferation requires the participation of accessory cells (AC) (e.g., macrophages); EL-4 cells are able to function as AC. These data indicate that ZDV synergizes with TMP-SMX, causing severe hematotoxicity and suppressing AC-dependent immune function, and suggest that this therapeutic regimen may contribute to the immune deterioration in AIDS patients.