Human immunodeficiency virus glycoprotein 160 induces cytokine mRNA expression in the rat central nervous system

1. Elevated proinflammatory cytokines within the central nervous system (CN S) of individuals infected with human immunodeficiency virus (HIV) may cont ribute to altered CNS processes prior to the onset of AIDS. Most studies of HIV-induced alterations in cytokine expression within the CNS have focused on interleukin (IL)-1 and tumor necrosis factor (TNF). 2. We used a ribonuclease protection assay (RPA) to elucidate further the p attern of cytokine mRNA expression in the rat CNS in response to HIV envelo pe glycoprotein 160 (gp160). Male Sprague-Dawley rats were surgically impla nted with a guide cannula directed into a lateral cerebral ventricle. HIV g p160 was injected intracerebroventricularly and rats were sacrificed immedi ately (time = 0) or at 1, 2, or 4 hr postinjection. Discrete brain regions were dissected, and peripheral glands removed. All tissues were frozen in l iquid nitrogen until RNA extraction and assay. 3. IL-1 beta, IL-1 alpha, TNF-alpha, and TNF beta mRNAs were constitutively expressed in brain tissues. Central administration of gp160 dramatically i ncreased mRNA expression for IL-1 beta and TNF-alpha in the hypothalamus, h ippocampus, brainstem, and cerebellum. Furthermore, although mRNA expressio n for IL-5, IL-6, and IL-10 was never detected under basal conditions, thes e mRNAs were increased in brain tissue after administration of gp160. Peak expression in each brain region was detected 2 hr after administration. Mul tiple cytokine mRNAs were detected in peripheral tissues, but their express ion was not altered by central administration of gp160. 4. Our results indicate that gp160 induces mRNA expression in brain for cyt okines other than IL-1 and TNF. Screening for multiple cytokine mRNA in thi s manner provides extensive information concerning the particular cytokines that may be involved in T-HIV-induced pathologies and alterations in CNS p rocesses.