INTRACEREBRAL HIV GLYCOPROTEIN (GP120) ENHANCES TUMOR-METASTASIS VIA CENTRALLY RELEASED INTERLEUKIN-1

Infection with the human immunodeficiency virus (HIV) is associated wi th a high incidence of cancers. This relationship does not appear to b e due to a direct effect of the virus, and may be mediated by neuroimm une interactions since the HIV glycoprotein, gp120, enters the brain s oon after infection with HIV, and intracerebroventricular (i.c.v.) inf usion of gp120 suppresses aspects of cellular and tumor immunity, It h as been speculated that this suppression may be attributed to the rele ase of interleukin-1 (IL-1) in the brain induced by gp120. Using an in vivo tumor model, we examined the effect of centrally administered gp 120 on tumor metastasis and lung clearance of mammary adenocarcinoma ( MADB106) tumor cells in rats, and the role played by brain IL-1 in med iating these effects. We demonstrate that central administration of gp 120 (4 mu g) significantly (p < 0.05) increased the retention of tumor cells in the lungs and significantly (p < 0.02) enhanced the developm ent of tumor metastases. Central administration of IL-1 beta (10 ng) a lso significantly (p < 0.05) increased retention of tumor cells in the lungs, The effect of gp120 on lung retention of tumor cells was block ed 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 mu g). Given that systemic a dministration of gp120 or IL-1 beta had no effect on the retention of tumor cells in the lungs, these findings indicate that gp120-induced s ecretion of IL-1 within the brain most likely mediates the effects of gp120 on tumor metastasis. These findings suggest a possible neuroimmu ne mechanism to account for the increased incidence and aggressiveness of tumors in HN-infected patients. (C) 1998 Elsevier Science B.V.