Induction of bone‐marrow eosinophilia in mice submitted to surgery is dependent on stress‐induced secretion of glucocorticoids

We examined bone‐marrow in mice receiving subcutaneous implants of heat‐coagulated egg white, which are known to present chronic eosinophilic inflammation at the implant site. Egg white implants (EWIs) induced marked bone‐marrow eosinophilia, and increased bone‐marrow cell responses to granulocyte‐macrophage colony‐stimulating factor and interleukin‐5 in culture. These effects were observed as early as 24 h and lasted for, at least, 30 days in implant recipients. We found, however, that increased eosinophil production was also observed in control mice which underwent surgery but received no EWI (sham‐implanted mice), up to 15 days post‐surgery. As this suggests an important contribution of nonspecific stress mechanisms to eosinopoiesis, we further evaluated the role of stress hormones produced by the adrenal glands in the bone‐marrow eosinophilia of sham‐implanted mice. Bone‐marrow eosinophilia in mice undergoing surgery was dissociated from increases in other haemopoietic lineages. Surgery by itself increased circulating corticosterone levels by 24 h, and the increase was prevented by inhibition of adrenal glucocorticoid production by metyrapone. The effect of surgery on bone‐marrow eosinophilia was prevented by pretreatment with both the glucocorticoid receptor antagonist, mifepristone, and metyrapone, and by surgical adrenalectomy. By contrast, cathecolamine receptor antagonists (propranolol, prazosin and yohimbine) were ineffective, indicating that cathecolamine release from the adrenal glands was not responsible for the effects on bone‐marrow. These results highlight a critical role for stress‐induced glucocorticoid hormones in selectively upregulating bone‐marrow eosinopoiesis in mice submitted to surgery. British Journal of Pharmacology (2004) 143, 541–548. doi:10.1038/sj.bjp.0705943