Intracerebroventricular infusion of interleukin 1 rapidly decreases peripheral cellular immune responses.
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.
Sundar
S K
SK
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710.
Becker
K J
KJ
Cierpial
M A
MA
Carpenter
M D
MD
Rankin
L A
LA
Fleener
S L
SL
Ritchie
J C
JC
Simson
P E
PE
Weiss
J M
JM
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
D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D000521:alpha-MSH