Immunopharmacology of thymosin α1 and cytokine synergy
Immunopharmacology of thymosin α1 and cytokine synergy
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DOI：
10.1196/annals.1415.036
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Hadden, John W.
中科院分区：
文献类型：
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作者：
Naylor, Paul H.;Quadrini, Karen;Hadden, John W.
胸腺素α 1（T α 1）是一种28个氨基酸的生物活性蛋白，从前体蛋白胸腺素α原的2-29位裂解。自发现以来，T α 1已在各种环境中施用于动物和人类，其药理作用是增强细胞免疫。T α 1给药在辐射、化疗、肿瘤负荷或免疫衰老导致T细胞数量和/或功能减少的情况下非常有效。最近的体外研究，包括本文报道的研究，表明T α 1可能通过各种细胞因子常用的途径起作用。这提高了T α 1和细胞因子可能通过T α 1增强细胞因子活性而具有协同活性的可能性。先前已经报道了用T α 1和高剂量IL-2治疗荷瘤小鼠时对肿瘤生长的改善控制。我们用刘易斯肺癌小鼠模型扩展了这些研究，使用IRX-2，一种含有多种细胞因子的天然定义明确的生物制剂，与T α 1（IRX-3）组合。尽管IRX-2单独使用是有效的（使用比大多数典型研究中含有显著更少IL-2的剂量），但添加T α 1导致荷瘤小鼠的存活率显著改善。基于这些观察结果，T α 1的免疫药理学预测，当与细胞因子联合使用时，T α 1在恢复细胞免疫活性方面具有重要的临床作用。由于存在肿瘤、放疗和/或化疗或宿主衰老而经历免疫抑制的患者将最受益于该治疗组合。
Thymosin alpha 1 (T alpha 1) is a 28 amino acid biologically active protein cleaved from positions 2-29 of a precursor protein, prothymosin alpha. Since its discovery, T alpha 1 has been administered to animals and humans in a wide variety of settings and its pharmacologic effects are to enhance cellular immunity. T alpha 1 administration is highly effective in settings where irradiation, chemotherapy, tumor burden, or immune senescence have caused a reduction of T cell number and/or function. Recent in vitro studies, including the one reported here, suggest that T alpha 1 may act via pathways commonly used by various cytokines. This raises the possibility that T alpha 1 and cytokines may have synergistic activity through potentiation of cytokine activity by T alpha 1. Improved control of tumor growth when tumor-bearing mice were treated with T alpha 1 and high doses of IL-2 has been previously reported. We extended those studies with the Lewis lung carcinoma mouse model using IRX-2, a natural welldefined biologic containing multiple cytokines, in combination with T alpha 1 (IRX-3). Although IRX-2 was effective alone (using doses that contain significantly less IL-2 than in most typical studies), adding T alpha 1 led to significant improvement in survival of the tumor-bearing mice. Based on these observations, the immunopharmacology of T alpha 1 predicts an important clinical role for T alpha 1 in the restoration of cellular immune activity when used in combination with cytokines. Patients who experience immune suppression due to the presence of tumor, irradiation, and/or chemotherapy or aging of the host would most benefit from this treatment combination.