Suppression of in vitro antibody production by corticotropin-releasing factor neurohormone

Abstract

Corticotropin-releasing factor (CRF) is a peptide hormone that regulates the synthesis of pro-opiomelanocortin (POMC)-derived bioactive peptides from the cells of both neuroendocrine system and immune system. In this study, the effect of CRF on in vitro production of antibodies was investigated. The peripheral blood mononuclear cells (MNC), at a concentration of 1 × 10 6 cells ml −1, from several healthy blood donors were stimulated to produce immunoglobulins with 25 μg ml −1 pokeweed mitogen (PWM) in the presence of different concentrations of CRF (10 −16 to 10 −7 M range). After 7 days of incubation, the cell cultures were centrifuged, and the supernatants quantified for IgG, IgM, and IgA by enzyme-linked immunosorbent assay (ELISA). At concentrations of 10 −13 M or greater, the CRF and three structurally related peptides (Tyr-CRF, α-helical CRF 9−41, and sauvagine) caused a statistically significant ( P < 0.001) suppression of the production of all three isotypes of Ig. At a antagonist: agonist ratio of as high as 100:1, the antagonist α-helical CRF 9−41 did not antagonize the inhibitory action of CRF, instead it showed synergism with CRF by accentuating the CRF-induced suppression of IgG synthesis. This unexpected result may be due to the involvement of a subtype of CRF receptor which is insensitive to α-helical CRF. Moreover, the production of all three Ig isotypes was suppressed by rabbit antihuman-interleukin-1 (anti-IL-1) or rabbit antihuman-β-endorphin (anti-βE) or monocyte-depeletion, but neither treatment significantly modified the CRF-induced suppression of antibody production. These indirect studies suggest that the B cell response factors other than the IL-1 and βE may be involved in the mechanism of action of CRF-induced suppression of PWM-stimulated antibody production by human MNC.