Article
G-CSF suppresses allergic pulmonary inflammation, downmodulating cytokine, chemokine and eosinophil production
Registro en:
QUETO, Tulio et al. G-CSF suppresses allergic pulmonary inflammation, downmodulating cytokine, chemokine and eosinophil production. Life Science, Oxford, v. 88, n. 19-20, 2011.
2252-6277
10.1016/j.lfs.2011.03.001
Autor
Queto, Túlio
Vasconcelos, Zilton Farias Meira de
Luz, Ricardo Alves
Anselmo, Carina
Guiné, Ana Amélia A.
Silva, Patricia Machado R.
Farache, Júlia
Cunha, José Marcos T.
Bonomo, Adriana C.
Elsas, Maria Ignez Capella Gaspar
Xavier-Elsas, Pedro Paulo
Resumen
INCA, CNPq, FIOCRUZ AIMS: Granulocyte Colony-Stimulating Factor (G-CSF), which mobilizes hemopoietic stem cells (HSC), is believed to protect HSC graft recipients from graft-versus-host disease by enhancing Th2 cytokine secretion. Accordingly, G-CSF should aggravate Th2-dependent allergic pulmonary inflammation and the associated eosinophilia. We evaluated the effects of G-CSF in a model of allergic pulmonary inflammation. MAIN METHODS: Allergic pulmonary inflammation was induced by repeated aerosol allergen challenge in ovalbumin-sensitized C57BL/6J mice. The effects of allergen challenge and of G-CSF pretreatment were evaluated by monitoring: a) eosinophilia and cytokine/chemokine content of bronchoalveolar lavage fluid, pulmonary interstitium, and blood; b) changes in airway resistance; and c) changes in bone-marrow eosinophil production. KEY FINDINGS: Contrary to expectations, G-CSF pretreatment neither induced nor enhanced allergic pulmonary inflammation. Instead, G-CSF: a) suppressed accumulation of infiltrating eosinophils in bronchoalveolar, peribronchial and perivascular spaces of challenged lungs; and b) prevented ovalbumin challenge-induced rises in airway resistance. G-CSF had multiple regulatory effects on cytokine and chemokine production: in bronchoalveolar lavage fluid, levels of IL-1 and IL-12 (p40), eotaxin and MIP-1a were decreased; in plasma, KC, a neutrophil chemoattractant, was increased, while IL-5 was decreased and eotaxin was unaffected. In bone-marrow, G-CSF: a) prevented the increase in bone-marrow eosinophil production induced by ovalbumin challenge of sensitized mice; and b) selectively stimulated neutrophil colony formation. SIGNIFICANCE: These observations challenge the view that G-CSF deviates cytokine production towards a Th2 profile in vivo, and suggest that this neutrophil-selective hemopoietin affects eosinophilic inflammation by a combination of effects on lung cytokine production and bone-marrow hemopoiesis.