Upregulation by glucocorticoids of responses to eosinopoietic cytokines in bone-marrow from normal and allergic mice.
Since the production of eosinopoietic cytokines (GM-CSF, IL-3, IL-5) is inhibited by glucocorticoids, while responsiveness to these cytokines is enhanced in bone-marrow of allergic mice, we studied the ability of glucocorticoids to modulate murine bone-marrow eosinopoiesis. Progenitor (semi-solid) and/or precursor (liquid) cultures were established from bone-marrow of: (a) normal mice; (b) ovalbumin-sensitized and challenged 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, and numbers of eosinophil-peroxidase-positive cells were determined at day 7. In BALB/c mice, dexamethasone (10(-7) M) increased GM-CSF-stimulated myeloid colony formation (P = 0.01), as well as the frequency (P=0.01) and size (P<0.01) of eosinophil colonies. Dexamethasone (10(-7) M) alone had no effect. Dexamethasone (10(-7)-10(-10) M) increased (P<0.002) eosinophil precursor 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. Hydrocortisone 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). These effects were blocked by RU 486 (20 mg kg(-1), orally, 2 h before dexamethasone, or added in vitro at 10 microM, P<0.001). Glucocorticoids, acting in vivo or in vitro, through glucocorticoid receptors, enhance bone-marrow eosinopoiesis in naïve and allergic mice.
Gaspar Elsas
M I
MI
Depto. de Pesquisa, Instituto Fernandes Figueira, FIOCRUZ, Rio de Janeiro, Brazil. elsas@iff.fiocruz.br
Maximiano
E S
ES
Joseph
D
D
Alves
L
L
Topilko
A
A
Vargaftig
B B
BB
Xavier Elsas
P
P
D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001853:Bone Marrow / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006967:Hypersensitivity / Q000378:metabolism*; D007114:Immunization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone