O R I G I N A L A R T I C L E In humans, corticotropin releasing hormone antagonizes some of the negative immunoregulatory effects of serotonin

Both corticotropin releasing hormone (CRH) and serotonin (5-HT) participate in the stress response and are known to modulate cytokine release by human immune cells. Extracellular 5-HT concentrations at or above the serum values have negative immunoregulatory effects by inhibiting the production of interferon-γ (IFNγ), a pro-inflammatory cytokine produced by Th-1-like lymphocytes, whereas 5-HT has no significant effects on the production of interleukin-10 (IL10), an anti-inflammatory cytokine. In one study, CRH significantly decreases IFNγ production by cultured human peripheral blood immunocytes, whereas in other studies CRH increases the production of cytokines, such as IL-1, IL-2 and IL-6. The aims of the present study were to examine i) the effects of CRH, 10–9 M, 10–8 M and 10–7 M, on the stimulated production of IFNγ, IL-10 and tumor necrosis factor-α (TNFα) by human whole blood; and ii) whether CRH, 10–9 M, 10–8 M and 10–7 M, may antagonize some of the negative immunoregulatory effects of 5-HT, 1.5 µg/mL or 15 µg/mL. We found that CRH, 10–9 M, 10–8 M and 10–7 M, had no significant effects either on the stimulated production of IFNγ, IL-10 or TNFα or on the IFNγ/IL-10 production ratio, which reflects the pro-inflammatory capacity of the culture. 5-HT, 1,5 µg/dL and 15 µg/dL, significantly suppressed the production of IFN γ and TNFα and the IFNγ/IL-10 production ratio. CRH, 10–7 M, significantly reversed the 5-HT (1.5 µg/mL and 15 µg/mL)-induced suppression of IFNγ production. CRH at all concentrations significantly blocked the 5-HT (1.5 µg/mL and 15 µg/ mL)-induced suppression of TNFα production. The results suggest that CRH has no significant direct effects on the production of IFN γ, IL-10 and TNFα, but antagonizes the negative immunoregulatory effects of 5-HT on the production of IFNγ and TNFα and on the IFNγ/IL-10 production ratio.