Therapeutic application of zinc in human immunodeficiency virus against opportunistic infections
Therapeutic application of zinc in human immunodeficiency virus against opportunistic infections
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DOI：
10.1093/jn/130.5.1424s
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发表时间：
2000-05-01
影响因子：
4.2
通讯作者：
Muzzioli, M
中科院分区：
文献类型：
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作者：
Mocchegiani, E;Muzzioli, M
锌在抵抗病毒、真菌和细菌感染中的相关性是公认的，因为它在整个免疫系统的效率中起关键作用，特别是在赋予称为胸腺素的胸腺激素生物活性方面，胸腺素对T细胞系具有分化特性。在疾病的IV期（疾病控制和预防中心分类），活性胸腺肽（活性胸腺肽，ZnFTS）强烈减少，伴随着CD 4（+）细胞计数和锌血症值的减少。与此相反，非锌结合形式的胸腺素（非活性胸腺素，FTS）非常高。在体外添加锌的血浆样品诱导恢复的胸腺肽的活性形式，表明低锌的生物利用度作为受损的胸腺功能的原因，随之而来的CD 4（+）耗尽，复发机会性感染的发病率的危险因素的分析表明，CD 4+耗尽和锌缺乏有显着的分数。与齐多夫定（AZT）治疗相结合，在IV期补充锌1个月（45 mg Zn 2 +/d）可诱导活性锌结合胸腺肽、锌血症和CD 4（+）细胞的恢复，同时与AZT治疗组相比，复发机会性感染减少（50%）。补充锌后，观察到念珠菌或卡氏肺孢子虫的复发完全消失。HIV阳性锌治疗组的相对危险因素（CD 4（+）耗竭和锌缺乏）评分较低，因此证实了锌与涉及细胞外基质的机会性感染的相关性。新的HAART间接证实了这一假设，其中不会发生机会性感染。事实上，在HAART治疗的受试者中，HIV RNA与CD 4（+）和锌血症值呈负相关（r =-0.73，P < 0.01）。与AZT治疗的受试者相比，HAART治疗的受试者中出现机会性感染的相同相关因素评分较低。这些发现，一方面，显示AZT治疗与HAART治疗相比对HIV进展的疗效较差，但另一方面，它们表明HAART缺乏机会性感染的发生也可能是由于锌的生物利用度较高。这进一步支持了锌对HIV机会性感染的关键作用，可能是HIV或相关病原体的独立影响。
The relevance of zinc in resistance to infections by virus, fungi and bacteria is recognized because of its pivotal role in the efficiency of the entire immune system, in particular in conferring biological activity to a thymic hormone called thymulin, which has differentiation properties on T-cell lines, In infection with human immunodeficiency virus (HIV), the zinc-bound form of thymulin (active thymulin, ZnFTS) is strongly reduced in stage IV of the disease (Centers for Disease Control and Prevention classification) with concomitant decrements in CD4(+) cell count and zincemia values. The zinc-unbound form of thymulin (inactive thymulin, FTS) is, in contrast, very high. The in vitro addition of zinc to plasma samples induces a recovery of the thymulin active form, suggesting low zinc bioavailability as the cause of impaired thymic functions with consequent CD4(+) depletion, An analysis of risk factors for the incidence of recidivism opportunistic infections shows CD4+ depletion and zinc deficiency to have significant scores. Supplementation with zinc for 1 mo (45 mg Zn2+/d) associated with zidovudine (AZT) therapy in stage IV induces recovery of active zinc-bound thymulin, of zincemia, of CD4(+) cells with concomitant reduction (50%) of recidivism opportunistic infections compared with the AZT-treated group. Complete disappearance of recidivism by Candida aesophagea or Pneumocystis carinii is observed after supplementation with zinc. The relative risk factors (CD4(+) depletion and zinc-deficiency) have lower scores in the HIV-positive zinc-treated group, confirming, as such, the relevance of zinc in opportunistic infections that involve extracellular matrix. Such an assumption is indirectly confirmed with new HAART, where no opportunistic infections occur. Indeed, HIV RNA is inversely correlated with both CD4(+) and zincemia values (r = -0.73, P < 0.01) in HAART-treated subjects, Lower scores for the same relative factors for the appearance of opportunistic infections are present in HAART-treated subjects compared with those treated with AZT. These findings, on the one hand, show the poor efficacy of AZT therapy compared with HAART therapy for the progression of HIV, but on the other hand, they suggest that the lack of occurrence of opportunistic infections by HAART may also result from major zinc bioavailability. This further supports the key role played by zinc against opportunistic infections in HIV with a possible independent effect by either HIV or the pathogens involved.