ovalbumin and Bone-Marrow-Diseases

Interleukin (IL)-9 is a Th2-derived cytokine with pleiotropic biological effects, which recently has been proposed as a candidate gene for asthma and allergy. We aimed to evaluate the therapeutic effect of a neutralizing anti-IL-9 antibody in a mouse model of airway eosinophilic inflammation and compared any such effect with anti-IL-5 treatment.. OVA-sensitized Balb/c mice were intraperitoneally pretreated with a single dose (100 microg) of an anti-mouse IL-9 monoclonal antibody (clone D9302C12) or its vehicle. A third group was given 50 microg of a monoclonal anti-mouse IL-5 antibody (TRFK-5) or its vehicle. Animals were subsequently exposed to OVA on five days via airways. Newly produced eosinophils were labelled using 5-bromo-2'-deoxyuridine (BrdU). BrdU+ eosinophils and CD34+ cell numbers were examined by immunocytochemistry. After culture and stimulation with OVA or PMA+IC, intracellular staining of IL-9 in bone marrow cells from OVA-exposed animals was measured by Flow Cytometry. The Mann-Whitney U-test was used to determine significant differences between groups.. Anti-IL-9 significantly reduced bone marrow eosinophilia, primarily by decrease of newly produced (BrdU+) and mature eosinophils. Anti-IL-9 treatment also reduced blood neutrophil counts, but did not affect BAL neutrophils. Anti-IL-5 was able to reduce eosinophil numbers in all tissue compartments, as well as BrdU+ eosinophils and CD34+ progenitor cells, and in all instances to a greater extent than anti-IL-9. Also, FACS analysis showed that IL-9 is over-expressed in bone marrow CD4+ cells after allergen exposure.. Our data shows that a single dose of a neutralizing IL-9 antibody is not sufficient to reduce allergen-induced influx of newly produced cells from bone marrow to airways. However, in response to allergen, bone marrow cells over-express IL-9. This data suggest that IL-9 may participate in the regulation of granulocytopoiesis in allergic inflammation.

Topics: Animals; Bone Marrow Cells; Bone Marrow Diseases; Interleukin-5; Interleukin-9; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Pulmonary Eosinophilia; Respiratory Hypersensitivity

Immunostimulatory DNA sequences (ISS) inhibit eosinophilic inflammation and airway hyperreactivity in mouse models of asthma. In vitro ISS activate natural killer (NK) cells to secrete IFN-gamma, and this cytokine is hypothesized to contribute to the antiallergic effect of ISS in vivo.. We investigated whether ISS activation of NK cells is important in mediating the reduction in airway hyperreactivity and the antieosinophilic effect of ISS in vivo.. We assessed whether ISS modulated the development of eosinophilic airway inflammation and airway hyperreactivity to methacholine in ovalbumin (OVA)-sensitized and OVA allergen-challenged mice pretreated with an antibody to deplete NK cells.. Mice sensitized and challenged with OVA had significant bronchoalveolar lavage and lung eosinophilia, as well as airway hyperresponsiveness. ISS induced significant inhibition of bronchoalveolar lavage and lung eosinophilia, as well as airway hyperresponsiveness, in OVA-sensitized mice pretreated before OVA challenge with an NK cell-depleting antibody (NK(-) mice), as well as in mice pretreated with a control non-NK cell-depleting antibody (NK(+) mice). The NK cell-depleting antibody inhibited ISS-induced IFN-gamma production by spleen cells.. These studies demonstrate that depletion of NK cells has no significant effect on ISS-mediated inhibition of airway eosinophilia and airway hyperresponsiveness in vivo, suggesting that non-NK cells and cytokines other than IFN-gamma derived from NK cells mediate the majority of the ISS-inhibitory effect on eosinophilic inflammation and airway hyperresponsiveness in vivo.

Topics: Adjuvants, Immunologic; Animals; Asthma; Bone Marrow Diseases; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Cells, Cultured; DNA; Eosinophilia; Female; Interferon-gamma; Killer Cells, Natural; Lymphocyte Depletion; Methacholine Chloride; Mice; Mice, Inbred C57BL; Ovalbumin; Pulmonary Eosinophilia

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents; Blood Cell Count; Blood Platelets; Body Weight; Bone Marrow Diseases; Bone Marrow Examination; Fibrous Dysplasia of Bone; Hemoglobinometry; Leukocyte Count; Liver; Ovalbumin; Oxyphenbutazone; Phenylbutazone; Prednisolone; Pyrazoles; Rabbits; Reticulocytes; Spleen