Chukwuocha R U, Reyes E, Tokuda S
Department of Microbiology, University of New Mexico School of Medicine, Albuquerque.
Int J Immunopharmacol. 1994 Mar;16(3):205-15. doi: 10.1016/0192-0561(94)90014-0.
We have previously reported that met-enkephalin has dual immunomodulatory properties in vitro. We have continued this investigation using an in vivo system. In this study, Alzet miniosmotic pumps were loaded with either met-enkephalin, DTLET or FK 33-824 and were surgically implanted into BAF1/J mice. Twenty-four hours after pump implantation, mice were challenged with sub-optimal, optimal or supraoptimal immunizing doses of antigen. The immune response was assessed 4 or 5 days after primary immunization. FK 33-824, a met-enkephalin analogue, had no effect on the response of mice challenged with a suboptimal antigen dose. However, FK 33-824, at a pump concentration of 10(-3) M, suppressed the response against optimal challenge doses of antigen. At a pump concentration of 10(-8) M, FK 33-824 suppressed, enhanced or had no effect on the supraoptimal antigen dose-induced immune response. The suppressive effect of FK 33-824 in mice immunized with either optimal or supraoptimal doses of antigen was blocked by naloxone. Met-enkephalin and its delta opioid receptor specific analogue, DTLET, had no effect on the immune response to optimal antigen immunization. These results indicate that FK 33-824 has in vivo immunomodulatory activity and provide evidence that opioid peptides may either upregulate or downregulate the in vivo immune response depending on the strength of the response.
我们之前曾报道过，甲硫氨酸脑啡肽在体外具有双重免疫调节特性。我们使用体内系统继续了这项研究。在本研究中，将Alzet微量渗透泵装载甲硫氨酸脑啡肽、DTLET或FK 33 - 824，然后通过手术植入BAF1/J小鼠体内。泵植入24小时后，用次优、最优或超优免疫剂量的抗原对小鼠进行攻击。在初次免疫后4或5天评估免疫反应。甲硫氨酸脑啡肽类似物FK 33 - 824对用次优抗原剂量攻击的小鼠的反应没有影响。然而，泵浓度为10(-3) M的FK 33 - 824抑制了针对最优攻击剂量抗原的反应。在泵浓度为10(-8) M时，FK 33 - 824对超优抗原剂量诱导的免疫反应有抑制、增强或无影响。纳洛酮可阻断FK 33 - 824对用最优或超优剂量抗原免疫的小鼠的抑制作用。甲硫氨酸脑啡肽及其δ阿片受体特异性类似物DTLET对最优抗原免疫的免疫反应没有影响。这些结果表明FK 33 - 824具有体内免疫调节活性，并提供了证据表明阿片肽可能根据反应强度上调或下调体内免疫反应。
