Regulation of bone marrow and airway CD34+ eosinophils by interleukin-5

Abstract

The aim of this study was to evaluate the effect of a neutralizing anti-interleukin (IL)-5 monoclonal antibody (TRFK-5) on bone marrow and airway CD34(+) and immature eosinophils. A focus was to determine the effect of the timing of treatment. Balb/c mice were ovalbumin-sensitized and subsequently exposed to ovalbumin for 5-10 d via airway route. Animals were treated intraperitoneally with TRFK-5 or its isotype control (50 microg) once at different time points. Newly produced eosinophils were labeled using 5-bromo-2'-deoxyuridine (BrdU). BrdU(+) and CD34(+) eosinophil numbers were examined by immunocytochemistry. TRFK-5 reduced bone marrow immature eosinophils within 3 d. This effect was closely related to a reduction of BrdU(+) and CD34(+) bone marrow eosinophils, and reduced numbers of blood eosinophils. However, bronchoalveolar lavage (BAL) eosinophilia was not attenuated to the same degree. The effect of TRFK-5 was most prominent in the extended allergen-exposure protocol, where the treatment was given in the middle of the exposure, with strongly reduced bone marrow CD34(+) and immature bone marrow eosinophils, blood eosinophils as well as BAL BrdU(+) eosinophils, and BAL CD34(+) eosinophils. These data argue that anti-IL-5 downregulates eosinophilopoiesis within 3 d by action in the bone marrow, by inhibition of the early stages of eosinophil maturation from CD34(+) cells.