Effect of foot shock stress on the interferon-γ production of murine intestinal intraepithelial lymphocytes

To investigate the effect of stress on interferon (IFN)-γ production by intestinal intraepithelial lymphocytes (IEL), we exposed male C3H/HeN mice to electric foot shock for 30 min a day for 5 consecutive days. Immediately after the final foot shock stress, IEL from small intestine were isolated by Percoll density gradient. The stress induced a marked suppression of IFN-γ production by IEL stimulated with immobilized anti-CD3 mAb and a marked decrease in the proportion of IFN-γ-producing CD3⁺ IEL or αβTCR⁺ IEL stimulated with PMA + ionomycin. The αβTCR⁺ subset was the major cause of stress-induced suppression of IFN-γ production by IEL. Glucocorticoid induced the suppression of IFN-γ production by IEL in vitro, which was reversed by mifepristone (RU486), a glucocorticoid receptor antagonist. In vivo administration of RU486 reversed the stress-induced suppression of IFN-γ production by IEL. In conclusion, repeated foot shock stress suppressed IFN-γ production of IEL by stress-induced elevation of endogenous glucocorticoid. Substantial suppression of the αβTCR⁺ subset was the major cause of the suppression.