SummaryThere are lines of evidence that natural killer (NK) cells are sensitive to physical and psychological stress. Alterations in the immune system including NK cells are known to differ among tissues and organs. The effect of stress on the lung immune system, however, has not been well documented in spite of the fact that the lungs always confront viral or bacterial attacks as well as tumour cell metastasis. In this study, we intended to investigate the effect of restraint stress on lung lymphocytes including NK cells. C57BL/6 mice were exposed to 2 h restraint stress. The concentration of plasma epinephrine significantly rose immediately after the release from restraint as compared to home-cage control mice. Flow cytometric analysis revealed that the numbers of most lymphocyte subsets including NK cells were decreased in the lungs and blood but not in the spleen, immediately after restraint stress. Immunohistochemical examination revealed that the number of NK cells was decreased in the intraparenchymal region of the lungs, while the number of alveolar macrophages did not change. The decrease in the number of NK cells in the lungs and blood was reversed by the administration of propranolol, a nonselective beta adrenergic antagonist. Taken together, our findings suggest that acute stress reduces the number of intraparenchymal lung NK cells via activation of beta adrenergic receptors.

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Intestinal intraepithelial lymphocytes (IEL), one of the major effector components in the mucosal immune system, are phenotypically and functionally distinct from thymic and peripheral T cells. To investigate the effect of repeated stress on the number and function of IEL, we exposed male C3H/HeN mice to mild electric foot shock for 30 min/day for 5 consecutive days. Immediately after the final foot shock stress, the blood, spleen, thymus and small intestine of each of the mice were obtained. As a functional measure, we evaluated interferon (IFN)-γ production by IEL, since IFN-γ is a key immunomodulating cytokine in mucosal immune responses. Serum corticosterone level was elevated immediately after foot shock stress. There were no significant changes in the number of whole IEL and CD3 + IEL subsets after the stress. In contrast, the stress led to a significant decrease in the total number of thymocytes, particularly the reduction in the number of CD4 + CD8 + thymocytes. Thymocytes expressed the highest level of intracellular glucocorticoid receptor (GR), followed by splenocytes and IEL. The foot shock stress induced a marked suppression of IFN-γ production by IEL, when stimulated with immobilized anti-CD3 monoclonal antibody. Furthermore, corticosterone suppressed the IFN-γ production by cultured IEL, which was prevented by Mifepristone (RU486), a GR antagonist. In summary, repeated foot shock stress did not alter the numbers of IEL and CD3 + IEL subsets, but suppressed IFN-γ production by IEL, which was probably mediated by the elevated corticosterone. We therefore propose that stress influences host defense by suppressing the production of IFN-γ in IEL.stress; intestinal intraepithelial lymphocytes; interferon-γ ; corticosterone