Chang S L, Kenigs V, Moldow R L, Zadina J E
Department of Biology, Seton Hall University, South Orange, New Jersey 07079, USA.
Adv Exp Med Biol. 1995;373:201-8. doi: 10.1007/978-1-4615-1951-5_28.
Interleukin-1 beta (IL-1 beta) is a key mediator of immunological and pathological responses to stress, injury and disease and it has been suggested to have profound effects on neuroendocrine-immune functions. We have shown that central treatment with IL-I beta induces the expression of FOS proto-oncogene protein immunoreactivity (FOS-IR) in several hypothalamic nuclei including the paraventricular nucleus (PVN). Since FOS expression has been used as an anatomical marker of neuronal function, these results suggested that the involvement of IL-1 beta in the neuro-endocrine-immune axis may be mediated through the PVN. Treatment with several substances of abuse has been shown to modify immune function in vivo and in vitro. In this study, we compared the effects of morphine, ethanol and cocaine on IL-1 beta induction of FOS-IR in the rat hypothalamus. Acute treatment with morphine or ethanol induced FOS-IR in several nuclei including the PVN. Cocaine, which induced FOS-IR in the Caudate-Putamen (CPU), nucleus Accumbens (nAcc) and Locus Coeruleus (LC), however, did not induce FOS-IR in the PVN. Chronic treatment with morphine desensitized FOS responsiveness to morphine and IL-1 beta in the PVN since FOS-IR was no longer induced by IL-1 beta or morphine in the PVN after this treatment. Similarly, chronic ethanol treatment desensitized FOS responsiveness to ethanol and to IL-1 beta in the PVN. By contrast, chronic cocaine did not affect FOS responsiveness to IL-1 beta in the PVN even though the treatment was able to desensitize the FOS responsiveness to acute cocaine in the CPU, nAcc, and LC. These results suggest that the PVN may be a site where actions of IL-1 beta converge with those of morphine and ethanol, but not cocaine, to modulate neuro-endocrine-immune functions.
白细胞介素-1β（IL-1β）是对应激、损伤和疾病产生免疫和病理反应的关键介质，有人认为它对神经内分泌免疫功能有深远影响。我们已经表明，中枢给予IL-1β可诱导包括室旁核（PVN）在内的几个下丘脑核中FOS原癌基因蛋白免疫反应性（FOS-IR）的表达。由于FOS表达已被用作神经元功能的解剖学标志物，这些结果表明IL-1β在神经内分泌免疫轴中的作用可能是通过PVN介导的。已表明使用几种滥用物质进行治疗可在体内和体外改变免疫功能。在本研究中，我们比较了吗啡、乙醇和可卡因对大鼠下丘脑IL-1β诱导FOS-IR的影响。急性给予吗啡或乙醇可在包括PVN在内的几个核中诱导FOS-IR。然而，可卡因虽可在尾状壳核（CPU）、伏隔核（nAcc）和蓝斑（LC）中诱导FOS-IR，但在PVN中却不能诱导FOS-IR。慢性给予吗啡使PVN中FOS对吗啡和IL-1β的反应性脱敏，因为在此治疗后，PVN中不再由IL-1β或吗啡诱导FOS-IR。同样，慢性乙醇治疗使PVN中FOS对乙醇和IL-1β的反应性脱敏。相比之下，慢性可卡因治疗虽能使CPU、nAcc和LC中FOS对急性可卡因的反应性脱敏，但并未影响PVN中FOS对IL-1β的反应性。这些结果表明，PVN可能是IL-1β与吗啡和乙醇（而非可卡因）的作用汇聚以调节神经内分泌免疫功能的部位。
