Widespread activation and consequences of interleukin-1 in the brain.

The results described herein indicate that elevation of IL-1 in rat brain, either by infusion of IL-1 into the brain or by stimulation of release of endogenous IL-1 in the brain by LPS, rapidly suppresses a variety of immune responses measured in peripheral lymphocytes. This effect can be blocked by infusion of alpha-MSH into brain, an attribute that was used to indicate that the effects of LPS infusion occurred by stimulation of endogenous IL-1 and not some other influence of LPS. That suppression of cellular immune responses indeed describes the consequences of elevating IL-1 in brain was shown by determining the time course of effects and thereby demonstrating that rebound enhancement of cellular immune responses did not occur after either IL-1 or LPS. Studies that examined the mechanisms by which brain IL-1 affects immune responses indicated that IL-1 influences peripheral lymphocytes by stimulation of CRF in the central nervous system and that CRF in turn causes suppression of cellular immune responses through activation of both the pituitary-adrenal axis and the autonomic nervous system. These findings have also been observed in another laboratory. Moreover, Brown et al. have shown that IL-1 in brain suppresses macrophage function in addition to the suppression of lymphocyte functions described herein. The physiologic significance of IL-1 actions in the brain on immune responses remains to be determined, but the demonstration that this cytokine influences immune processes by acting in brain opens for study another means by which brain and immune system interact.