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

Abstract

1 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. 2 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. 3 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. 4 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. 5 These results highlight a critical role for stress-induced glucocorticoid hormones in selectively upregulating bone-marrow eosinopoiesis in mice submitted to surgery.

G-CSF suppresses allergic pulmonary inflammation, downmodulating cytokine, chemokine and eosinophil production

“…This hypothesis would be consistent with the observation that G-CSF only affected eosinophils in challenged animals, which generate this signal, unlike unchallenged controls (Gaspar Elsas et al 1997). Following our original demonstration by transfer experiments (Gaspar Elsas et al 1997), a number of defined stimuli have been shown to upregulate eosinophil production in vivo and in vitro, including glucocorticoids, either exogenously administered (Gaspar- Elsas et al 2009) or endogenously released from the adrenal glands of surgically stressed mice (Elsas et al 2004). However, while glucocorticoid-induced eosinophilopoiesis has been shown to be blocked by the glucocorticoid receptor antagonist, RU486 (mifepristone) (Gaspar- Elsas et al 2009), the nature of the mediator induced by allergen challenge remains undefined.…”

Evaluation of peroxisome proliferator‐activated receptor agonists on interleukin‐5‐induced eosinophil differentiation

“…However, in vitro studies have described a stimulatory effect of steroids on IL‐5‐induced colony formation . This phenomenon is observed in specific in vivo models, such as an acute stress model . Cyr et al .…”

Eosinophilopoiesis at the Cross-Roads of Research on Development, Immunity and Drug Discovery

“…Below, we review some of the current evidence about eosinophilopoiesis, including some of our own studies that also link eosinophils to surgical wounds [40], hoping to contribute to the ongoing debate on the physiological roles of eosinophils, for something can be learned about the value of a given cell type to the organism, from studying the conditions in which its development is fostered (or suppressed) by systemic influences, that presumably reflect the needs of the organism.…”