Favalli C, Mastino A, Jezzi T, Grelli S, Goldstein A L, Garaci E
Department of Experimental Medicine and Biochemistry, II University of Rome Tor Vergata, Italy.
Int J Immunopharmacol. 1989;11(5):443-50. doi: 10.1016/0192-0561(89)90172-0.
We have investigated the possibility of thymosin alpha 1 (TH) cooperating with alpha beta-interferon (IFN) in boosting natural killer (NK) activity in tumor-bearing, immunosuppressed mice in vivo. Treatment with a single injection of 30,000 IU of IFN 24 h before testing enhanced NK activity in tumor-bearing mice if the IFN was administered 9 days after tumor inoculation, when the animals have normal NK responsiveness. On the other hand, the same treatment led to lower or no improvement of NK responses if the treatment was given 13 or 17 days after tumor inoculation, at a time when tumor growth causes immunosuppression. However, combination treatment with TH (200 micrograms/kg) for 4 days, followed by IFN was found to restore normal NK cell activity. Selective depletion of antigen-positive cells showed that killer cells stimulated by combination treatment with TH and IFN seem to bear phenotypic characteristics of NK cells. These studies provide the first documentation of a novel combination approach to reconstitution of immunosuppressed tumor-bearing mice using TH and IFN. We hypothesize that TH restores NK boosting activity by IFN by effecting the differentiation/induction of precursor populations of IFN-responsive cells.
我们研究了胸腺素α1（TH）与αβ干扰素（IFN）协同作用，以增强荷瘤免疫抑制小鼠体内自然杀伤（NK）活性的可能性。在检测前24小时单次注射30,000 IU IFN进行治疗，若在肿瘤接种后9天给予IFN（此时动物具有正常的NK反应性），则可增强荷瘤小鼠的NK活性。另一方面，如果在肿瘤接种后13天或17天给予相同治疗（此时肿瘤生长导致免疫抑制），则NK反应降低或无改善。然而，发现先用TH（200微克/千克）治疗4天，然后给予IFN的联合治疗可恢复正常的NK细胞活性。抗原阳性细胞的选择性清除表明，TH和IFN联合治疗刺激的杀伤细胞似乎具有NK细胞的表型特征。这些研究首次记录了一种使用TH和IFN重建免疫抑制荷瘤小鼠的新型联合方法。我们假设TH通过影响IFN反应性细胞前体群体的分化/诱导来恢复IFN对NK的增强活性。
