Brain IL-1-induced immunosuppression occurs through activation of both pituitary-adrenal axis and sympathetic nervous system by corticotropin-releasing factor.
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.
Sundar
S K
SK
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710.
Cierpial
M A
MA
Kilts
C
C
Ritchie
J C
JC
Weiss
J M
JM
D000818:Animals; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D007074:Immunoglobulin G / Q000302:isolation & purification; D007165:Immunosuppression Therapy; D007375:Interleukin-1 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013154:Spleen / Q000276:immunology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D007074:Immunoglobulin G; D007375:Interleukin-1; D003346:Corticotropin-Releasing Hormone