PMID- 1662389 OWN - NLM STAT- MEDLINE DCOM- 19920207 LR - 20190501 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 88 IP - 24 DP - 1991 Dec 15 TI - Human immunodeficiency virus glycoprotein (gp120) infused into rat brain induces interleukin 1 to elevate pituitary-adrenal activity and decrease peripheral cellular immune responses. PG - 11246-50 AB - Intracerebroventricular (i.c.v.) infusion of glycosylated recombinant gp120, the envelope protein of human immunodeficiency virus, in various doses (100 ng to 4 micrograms) resulted in detection of interleukin 1 (IL-1) activity in a high percentage (61%; 33 of 54) of rat brains, whereas IL-1 was very rarely detected in brains of animals infused with several control substances (4%; 1 of 28). To detect IL-1, clarified glial lysate of diencephalon plus brainstem was subjected to gel exclusion chromatography and fractions were assessed for thymocyte stimulation. IL-1 was seen 2, 6, and 24 hr postinfusion. i.c.v. gp120 also produced known effects of IL-1 in brain, elevating steroid concentration in plasma and decreasing cellular immune responses [natural killer (NK) cell activity and mitogenic response to Con A] of blood and splenic lymphocytes. When gp120 was infused together with alpha-melanocyte-stimulating hormone (20 ng), which blocks many biological actions of IL-1, gp120 no longer elevated steroids or decreased NK cell activity. After intravenous gp120, IL-1 was not found in brain or plasma, indicating that stimulation of IL-1 in brain by i.c.v. gp120 was not due to gp120 affecting infiltrating cells from blood or to elevated circulating IL-1. That induction of IL-1 in brain might have resulted from lipopolysaccharide (LPS) in the gp120 solution was ruled out by studies showing that (i) heating of the infusion solution, which does not affect the capacity of LPS to induce IL-1, eliminated the ability of gp120 infusion to induce brain IL-1, and (ii) gp120 induced IL-1 in brains of LPS-resistant C3H/HeJ mice. Injection of gp120 directly into the hippocampus stimulated IL-1 more readily than i.c.v. infusion. Thymocyte stimulation produced by active fractions of gp120-infused brains was blocked by monoclonal antibody to IL-1 receptors. These findings indicate that elevation of IL-1 in brain can result from infection with human immunodeficiency virus and may be responsible for certain abnormalities (e.g., elevated activity of pituitary-adrenal axis) seen in AIDS patients. FAU - Sundar, S K AU - Sundar SK AD - Department of Psychiatry, Duke University Medical Center, Durham, NC 27710. FAU - Cierpial, M A AU - Cierpial MA FAU - Kamaraju, L S AU - Kamaraju LS FAU - Long, S AU - Long S FAU - Hsieh, S AU - Hsieh S FAU - Lorenz, C AU - Lorenz C FAU - Aaron, M AU - Aaron M FAU - Ritchie, J C AU - Ritchie JC FAU - Weiss, J M AU - Weiss JM LA - eng GR - MH45675/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (HIV Envelope Protein gp120) RN - 0 (Interleukin-1) RN - 581-05-5 (alpha-MSH) RN - W980KJ009P (Corticosterone) SB - IM MH - Animals MH - Brain/drug effects/*physiology MH - Cerebral Ventricles/drug effects/*physiology MH - Corticosterone/*blood MH - HIV Envelope Protein gp120/*administration & dosage/toxicity MH - Immunity, Cellular/*drug effects MH - Infusions, Intravenous MH - Infusions, Parenteral MH - Interleukin-1/biosynthesis/*physiology MH - Lymphocyte Activation MH - Male MH - Pituitary-Adrenal System/drug effects/*physiology MH - Rats MH - Rats, Inbred Strains MH - Reference Values MH - T-Lymphocytes/drug effects/*immunology MH - alpha-MSH/administration & dosage/*pharmacology PMC - PMC53111 EDAT- 1991/12/15 00:00 MHDA- 1991/12/15 00:01 PMCR- 1992/06/15 CRDT- 1991/12/15 00:00 PHST- 1991/12/15 00:00 [pubmed] PHST- 1991/12/15 00:01 [medline] PHST- 1991/12/15 00:00 [entrez] PHST- 1992/06/15 00:00 [pmc-release] AID - 10.1073/pnas.88.24.11246 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11246-50. doi: 10.1073/pnas.88.24.11246.