Journal of Neuroscience, Vol 10, 3701-3706, Copyright © 1990 by Society for Neuroscience
Brain IL-1-induced immunosuppression occurs through activation of both pituitary-adrenal axis and sympathetic nervous system by corticotropin- releasing factor
SK Sundar, MA Cierpial, C Kilts, JC Ritchie and JM Weiss
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710.
Intracerebroventricular infusion of femtomolar quantities of interleukin-1
(IL-1) or stimulated release of endogenous IL-1 in the brain suppresses
various cellular immune responses, decreasing natural killer cell (NK)
activity, response to mitogen, and interleukin-2 production of splenic and
blood lymphocytes (an effect hereafter called "brain IL-1-induced
immunosuppression"). The present study examines mechanisms by which IL-1
produces this effect. First, because IL-1 in the brain activates the
pituitary-adrenal axis by stimulating release of corticotropin-releasing
factor (CRF), the role of CRF was investigated. To block CRF,
affinity-purified antibody to CRF was infused into the lateral ventricle 30
min before introduction of IL-1. When this was done, suppression of
cellular immune responses that normally follow IL-1 infusion was completely
prevented. Infusion with an equal quantity of non-CRF IgG prior to IL-1 was
without effect. Second, the role of sympathetic nervous activity was
examined. To block neural transmission at sympathetic ganglia,
chlorisondamine (3.0 mg/kg) was injected intraperitoneally 60 min before
IL-1 infusion. When this was done, suppression of immune responses by IL-1
was partially blocked. These results indicate that IL-1 in the brain
suppresses various cellular immune responses by activating both the
pituitary- adrenal axis and the sympathetic nervous system, and that these
systems are both activated through the influence of IL-1 on CRF.
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