Hodgson D M, Yirmiya R, Chiappelli F, Taylor A N
Dept. of Neurobiology and Brain Research Institute, School of Medicine, University of California, Los Angeles, CA 90095, USA.
Brain Res. 1998 Jan 19;781(1-2):244-51. doi: 10.1016/s0006-8993(97)01243-2.
Infection with the human immunodeficiency virus (HIV) is associated with a high incidence of cancers. This relationship does not appear to be due to a direct effect of the virus, and may be mediated by neuroimmune interactions since the HIV glycoprotein, gp120, enters the brain soon after infection with HIV, and intracerebroventricular (i.c.v.) infusion of gp120 suppresses aspects of cellular and tumor immunity. It has been speculated that this suppression may be attributed to the release of interleukin-1 (IL-1) in the brain induced by gp120. Using an in vivo tumor model, we examined the effect of centrally administered gp120 on tumor metastasis and lung clearance of mammary adenocarcinoma (MADB106) tumor cells in rats, and the role played by brain IL-1 in mediating these effects. We demonstrate that central administration of gp120 (4 microg) significantly (p<0.05) increased the retention of tumor cells in the lungs and significantly (p<0.02) enhanced the development of tumor metastases. Central administration of IL-1beta (10 ng) also significantly (p<0.05) increased retention of tumor cells in the lungs. The effect of gp120 on lung retention of tumor cells was blocked by co-administration of alpha-melanocyte stimulating hormone (alpha-MSH, 20 ng), a hormone that blocks many of the biological effects of IL-1, or the IL-1 receptor antagonist (50 microg). Given that systemic administration of gp120 or IL-1beta had no effect on the retention of tumor cells in the lungs, these findings indicate that gp120-induced secretion of IL-1 within the brain most likely mediates the effects of gp120 on tumor metastasis. These findings suggest a possible neuroimmune mechanism to account for the increased incidence and aggressiveness of tumors in HIV-infected patients.
感染人类免疫缺陷病毒（HIV）与癌症的高发病率相关。这种关系似乎并非由病毒的直接作用所致，可能是由神经免疫相互作用介导的，因为HIV糖蛋白gp120在感染HIV后不久就会进入大脑，而脑室内（i.c.v.）注入gp120会抑制细胞免疫和肿瘤免疫的某些方面。据推测，这种抑制可能归因于gp120诱导大脑中白细胞介素-1（IL-1）的释放。我们使用体内肿瘤模型，研究了脑内给予gp120对大鼠乳腺腺癌（MADB106）肿瘤细胞的肿瘤转移和肺清除的影响，以及脑内IL-1在介导这些影响中所起的作用。我们证明，脑内给予gp120（4微克）显著（p<0.05）增加了肿瘤细胞在肺中的滞留，并显著（p<0.02）增强了肿瘤转移的发展。脑内给予IL-1β（10纳克）也显著（p<0.05）增加了肿瘤细胞在肺中的滞留。gp120对肿瘤细胞肺滞留的影响可被共同给予α-黑素细胞刺激素（α-MSH，20纳克）所阻断，α-MSH是一种能阻断IL-1许多生物学效应的激素，或IL-1受体拮抗剂（50微克）。鉴于全身给予gp120或IL-1β对肿瘤细胞在肺中的滞留没有影响，这些发现表明，gp120诱导脑内IL-1的分泌很可能介导了gp120对肿瘤转移的影响。这些发现提示了一种可能的神经免疫机制，以解释HIV感染患者肿瘤发病率增加和侵袭性增强的现象。
