Receptor-mediated immunomodulation by corticotropin-releasing factor.
In both normal and adrenalectomized rats, exogenous corticotropin-releasing factor (CRF) suppresses immune function, and stress-induced immunosuppression can be partially reversed with either CRF antibody or CRF antagonist, suggesting a role for CRF in immunomodulation. We now report binding of CRF to human monocyte-macrophages and T-helper lymphocytes but not to T-suppressor or B lymphocytes. Bound CRF was displaced by synthetic CRF as well as CRF antagonist. CRF binding at these sites was accompanied by increases in the concentration of cAMP (but not cGMP) in the cells, with minimal and maximal effective CRF doses of 10(-13) and 10(-6) M for the monocyte-macrophage and 10(-12) M and 10(-8) M for the T-helper cell. Production of cAMP in response to CRF was effectively inhibited by CRF antagonist in both cell types. Moreover, rat splenocyte proliferation induced by interleukin 2(IL-2; 110 IU) was blocked by CRF, half-maximally at a CRF dose of 2.2 x 10(-10) M and completely at 3.5 x 10(-9) M. Finally, when CRF was added together with a 50-fold molar excess of CRF antagonist the IL-2 effect was fully restored. This demonstration of specific, physiologically relevant CRF receptors on two key immunocytes, the monocyte-macrophage and the T-helper lymphocyte, along with in vitro immunosuppression concomitant with CRF binding reinforces the growing body of evidence for a prominent role for CRF in immunomodulation.
Audhya
T
T
Department of Medicine, New York University Medical Center, NY 10016.
Jain
R
R
Hollander
C S
CS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
D018019:Receptors, Corticotropin-Releasing Hormone; D017981:Receptors, Neurotransmitter; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D006152:Cyclic GMP