Rapid increase in bone-marrow eosinophil production and responses to eosinopoietic interleukins triggered by intranasal allergen challenge

Abstract

To define the effects of immunization and exposure to allergen on the eosinophil lineage, we studied blood and bone-marrow eosinophil numbers, serum interleukin (IL)-5 levels, and eosinophil progenitor and precursor responses to IL-3 and IL-5 in ovalbumin-immunized BALB/c mice after intranasal challenge. Increased blood eosinophilia was found in immune relative to nonimmune mice, but the differences between challenged and unchallenged immune animals were not significant. In contrast, significantly increased circulating levels of IL-5 and numbers of bone-marrow eosinophils were found in sensitized animals exposed to allergen, relative to unchallenged, sensitized controls. An allergen-induced increase in IL-3-sensitive progenitors yielding eosinophil-bearing colonies was also found at 2 h after challenge. Furthermore, an eosinophil differentiation assay showed a marked increase in the magnitude of the responses to IL-5 and IL-3 over a 7-day period in bone-marrow cells of sensitized animals, which was detectable at 24 h after allergen challenge, but not at 2 h and not in unchallenged controls. Modulation of the responses of bone-marrow cells to IL-5 is induced by a circulating factor present in challenged immune animals, as shown by in vivo plasma transfer, but is at best only partly blocked by in vivo treatment with the anti-IL-5 antibody TRFK-5. These data indicate that allergen challenge in the airways leads to rapid long-term modifications in bone-marrow eosinophil progenitors and precursors, and that increased responses to eosinopoietins in bone marrow depend on the release, between 2 h and 24 h after challenge, of a circulating factor distinct from IL-5.