Micg. Elsas et al., Upregulation by glucocorticoids of responses to eosinopoietic cytokines inbone-marrow from normal and allergic mice, BR J PHARM, 129(8), 2000, pp. 1543-1552
1 Since the production of eosinopoietic cytokines (GM-CSF, IL-3, IL-5) is i
nhibited by glucocorticoids, while responsiveness to these cytokines is enh
anced in bone-marrow of allergic mice, we studied the ability of glucocorti
coids to modulate murine bone-marrow eosinopoiesis.
2 Progenitor (semi-solid) and/or precursor (liquid) cultures were establish
ed from bone-marrow of: (a) normal mice; (b) ovalbumin-sensitized and chall
enged mice or (c) dexamethasone(1-5 mg kg(-1)) injected mice. Cultures were
established with GM-CSF (2 ng ml(-1)) or IL-5 (1 ng ml(-1)), respectively.
alone or associated with dexamethasone, hydrocortisone or corticosterone.
Total myeloid colony numbers, frequency and size of eosinophil colonies, an
d numbers of eosinophil-peroxidase-positive cells were determined at day 7.
3 In BALB/c mice, dexamethasone (10(-7) M) increased GM-CSF-stimulated myel
oid colony formation (P = 0.01), as well as the frequency (P = 0.01) and si
ze (P<0.01) of eosinophil colonies. Dexamethasone (10-7 M) alone had no eff
ect. Dexamethasone (10(-7)-10(-10) M) increased (P<0.002) eosinophil precur
sor responses to IL-5. Potentiation by dexamethasone was still detectable:
(a) on low density, immature, nonadherent BALB/c bone-marrow cells, (b) on
bone-marrow from other strains, and (c) on cells from allergic mice. Hydroc
ortisone and corticosterone had similar effects. Dexamethasone administered
in vivo, 24 h before bone-marrow harvest, increased subsequent progenitor
responses to GM-CSF (P=0.001) and precursor responses to IL-5 (P<0.001). Th
ese effects were blocked by RU 486 (20 mg kg(-1), orally, 2 h before dexame
thasone, or added in vitro at 10 mu M, P<0.001).
4 Glucocorticoids, acting in vivo or in vitro, through glucocorticoid recep
tors, enhance bone-marrow eosinopoiesis in naive and allergic mice.