On the action of cyclosporine A, rapamycin and tacrolimus on M. avium including subspecies paratuberculosis.
On the action of cyclosporine A, rapamycin and tacrolimus on M. avium including subspecies paratuberculosis.
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DOI：
10.1371/journal.pone.0002496
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发表时间：
2008-06-25
期刊：
影响因子：
3.7
通讯作者：
Brown ST
中科院分区：
文献类型：
--
作者：
Greenstein RJ;Su L;Juste RA;Brown ST
鸟分枝杆菌亚种副结核（MAP）可能是人畜共患的。近年来，“免疫调节剂”甲氨蝶呤、硫唑嘌呤、6-巯基嘌呤和“抗炎剂”5-ASA均被证明能在体外抑制MAP的生长。我们得出结论，它们最有可能的作用机制是作为抗ap抗生素。“免疫抑制剂”环孢素A、雷帕霉素和他克莫司（fk506）治疗多种“自身免疫性”和“炎症性”疾病。雷帕霉素和他克莫司属于大环内酯类。我们假设它们的作用模式可能只是抑制MAP的生长。环孢素A、雷帕霉素和他克莫司对人（Dominic & ucf4）、反刍动物（ATCC 19698 & 303）和鸟分枝杆菌亚种（ATCC 25291 & 101）培养MAP的MAP 14CO2辐射生长动力学的影响以“累积GI百分比下降”（%-ΔcGI）表示。阳性对照氯法齐明为99%-ΔcGI， 0.5µg/ml （Dominic）。阴性对照邻苯二胺对任何菌株均无剂量依赖性抑制作用。免疫抑制剂对MAP有剂量依赖性的抑制作用。环孢素的比例为97%-ΔcGI × 32µg/ml (Dominic)，雷帕霉素的比例为74%-ΔcGI × 64µg/ml (ucf4)，他克莫司的比例为43%-ΔcGI × 64µg/ml （ucf4）。我们展示了迄今为止未描述的“免疫抑制剂”在体外抑制MAP生长；环孢素A，大环内酯类药物雷帕霉素和他克莫司。这些数据与我们的论文一致，即在不知情的情况下，自1942年5-ASA和随后的硫唑嘌呤、6-巯基嘌呤和甲氨蝶呤被引入治疗一些“自身免疫性”和“炎症性”疾病以来，医学界一直在治疗MAP感染。
Mycobacterium avium subspecies paratuberculosis (MAP) may be zoonotic. Recently the “immuno-modulators” methotrexate, azathioprine and 6-MP and the “anti-inflammatory” 5-ASA have been shown to inhibit MAP growth in vitro. We concluded that their most plausible mechanism of action is as antiMAP antibiotics. The “immunosuppressants” Cyclosporine A, Rapamycin and Tacrolimus (FK 506) treat a variety of “autoimmune” and “inflammatory” diseases. Rapamycin and Tacrolimus are macrolides. We hypothesized that their mode of action may simply be to inhibit MAP growth. The effect on radiometric MAP 14CO2 growth kinetics of Cyclosporine A, Rapamycin and Tacrolimus on MAP cultured from humans (Dominic & UCF 4) or ruminants (ATCC 19698 & 303) and M. avium subspecies avium (ATCC 25291 & 101) are presented as “percent decrease in cumulative GI” (%-ΔcGI.) The positive control clofazimine has 99%-ΔcGI at 0.5 µg/ml (Dominic). Phthalimide, a negative control has no dose dependent inhibition on any strain. Against MAP there is dose dependent inhibition by the immunosuppressants. Cyclosporine has 97%-ΔcGI by 32 µg/ml (Dominic), Rapamycin has 74%-ΔcGI by 64 µg/ml (UCF 4) and Tacrolimus 43%-ΔcGI by 64 µg/ml (UCF 4) We show heretofore-undescribed inhibition of MAP growth in vitro by “immunosuppressants;” the cyclic undecapeptide Cyclosporine A, and the macrolides Rapamycin and Tacrolimus. These data are compatible with our thesis that, unknowingly, the medical profession has been treating MAP infections since 1942 when 5-ASA and subsequently azathioprine, 6-MP and methotrexate were introduced in the therapy of some “autoimmune” and “inflammatory” diseases.
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影响因子：
4.5
作者：
Caprilli, R;Angelucci, E;Vecchi, M
通讯作者：
Vecchi, M
影响因子：
9.8
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作者：
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