title: Intracerebroventricular infusion of interleukin 1 rapidly decreases peripheral cellular immune responses.
abstract: Low doses (50-200 pg or 3.1-12.4 fmol) of interleukin 1 (IL-1) infused into the brain of rats produced rapid suppression of various cellular immune responses in peripheral lymphocytes of rats. Fifteen minutes after infusion of purified IL-1 beta into the lateral ventricle, natural killer cell activity, response to phytohemagglutinin stimulation, and interleukin 2 production were markedly suppressed in lymphocytes isolated from blood and spleen. These effects were due to infusion of IL-1 into brain since they did not occur when IL-1 was infused into the cisterna magna (essentially posterior to brain) or was injected intraperitoneally. Effects of IL-1 in brain could be blocked by simultaneous infusion of alpha-melanocyte-stimulating hormone, which is known to block the biological actions of IL-1. To stimulate release of endogenous IL-1 in brain, lipopolysaccharide was infused; this produced similar effects as IL-1, and these effects also were blocked by alpha-melanocyte-stimulating hormone. At longer intervals after infusion of IL-1 and lipopolysaccharide (3, 6, and 24 hr), immune responses returned to baseline or remained suppressed; i.e., "rebound" immunopotentiation did not occur. Finally, IL-1 infusion suppressed cellular immune responses in adrenalectomized animals, thereby showing that the effects of central IL-1 on peripheral cellular immune responses were, at least in part, independent of the stimulatory effect of IL-1 on secretion of adrenal hormones. These results indicate a link from brain to peripheral immune responses by means of action of a cytokine acting in the brain.
authors.affiliation: Department of Psychiatry, Duke University Medical Center, Durham, NC 27710.
authors.forename: S K
authors.initials: SK
authors.lastname: Sundar
authors.forename: K J
authors.initials: KJ
authors.lastname: Becker
authors.forename: M A
authors.initials: MA
authors.lastname: Cierpial
authors.forename: M D
authors.initials: MD
authors.lastname: Carpenter
authors.forename: L A
authors.initials: LA
authors.lastname: Rankin
authors.forename: S L
authors.initials: SL
authors.lastname: Fleener
authors.forename: J C
authors.initials: JC
authors.lastname: Ritchie
authors.forename: P E
authors.initials: PE
authors.lastname: Simson
authors.forename: J M
authors.initials: JM
authors.lastname: Weiss
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D007111:Immunity, Cellular / Q000187:drug effects*; D007263:Infusions, Parenteral; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012016:Reference Values; D013997:Time Factors; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D000521:alpha-MSH