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Isolation of Brain-infiltrating Leukocytes
Published on: June 13, 2011
Intracerebroventricular infusion of interleukin 1 rapidly decreases peripheral cellular immune responses
S K Sundar1, K J Becker, M A Cierpial
1Department of Psychiatry, Duke University Medical Center, Durham, NC 27710.
Insights
Central interleukin-1 (IL-1) rapidly suppresses peripheral immune cell activity in rats. This brain-to-body immune signaling occurs independently of adrenal hormones and highlights cytokine action within the brain.
Area of Science:
- Neuroimmunology
- Cytokine Signaling
- Cellular Immunology
Background:
- The brain influences peripheral immune responses.
- Interleukin-1 (IL-1) is a key cytokine involved in immune regulation.
- Understanding central cytokine effects on peripheral immunity is crucial.
Purpose of the Study:
- To investigate the impact of central interleukin-1 (IL-1) administration on peripheral cellular immune responses in rats.
- To determine if IL-1 acting within the brain can suppress immune cell activity.
- To explore the mechanisms and independence of this neuro-immune communication.
Main Methods:
- Infusion of purified IL-1 beta into the rat lateral ventricle.
- Measurement of natural killer cell activity, phytohemagglutinin response, and IL-2 production in peripheral lymphocytes.
- Administration of IL-1 or lipopolysaccharide (LPS) into the cisterna magna or intraperitoneally for comparison.
- Blocking experiments using alpha-melanocyte-stimulating hormone (α-MSH).
- Assessment of immune responses in adrenalectomized rats.
Main Results:
- Intracerebroventricular IL-1 rapidly suppressed natural killer cell activity, phytohemagglutinin response, and IL-2 production in peripheral lymphocytes.
- These suppressive effects were specific to central administration and not observed with peripheral IL-1.
- Simultaneous α-MSH infusion blocked IL-1's suppressive effects, as did LPS-induced endogenous IL-1 release.
- Immune responses remained suppressed or returned to baseline without rebound potentiation.
- Central IL-1 effects persisted in adrenalectomized rats, indicating partial independence from adrenal pathways.
Conclusions:
- Cytokines acting within the brain, such as IL-1, can rapidly suppress peripheral cellular immune responses.
- This neuro-immune pathway is distinct from peripheral cytokine actions and partially independent of the adrenal axis.
- Findings reveal a significant link between central cytokine signaling and peripheral immune function.
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.

