Local and systemic responses in murine experimental allergic airways inflammation: mechanisms linking rhinitis to asthma

<b>Rationale</b> Recruitment of eosinophils to the airways, involving maturation and trafficking of eosinophil-basophil progenitors (EoB-CFU), is mainly regulated by interleukin (IL)-5 and eotaxin, but whether hemopoietic mechanisms are responsible for linkages between upper and lower airway inflammation has not yet been fully clarified.<p></p> <b>Methods</b> BALB/c mice sensitized and challenged to ovalbumin (OVA) were used to establish isolated upper (UAI), isolated lower (LAI), or combined upper and lower airway inflammation (ULAI).<p></p> <b>Results</b> Airways eosinophils and CD4+ cells were increased significantly: in nasal mucosa in UAI and ULAI mice, and in lung tissue in LAI and ULAI groups. IL-5 and eotaxin were increased significantly in nasal lavage fluid (NL) in UAI and ULAI mice, and in bronchial-alveolar lavage fluid (BAL) in LAI and ULAI groups. Numbers of recombinant-mouse IL-5 stimulated marrow EoB-CFU were significantly higher than control (23.0 ± 4.0) in all treatment groups (87.2 ± 9.6, 70.9 ± 5.4 and 56.5 ± 7.6 per 105 mononuclear cells plated, UAI, LAI and ULAI groups, respectively), but peaked much earlier (by 12 hrs after OVA challenge) in the ULAI group. Kinetic studies revealed that IL-5 and eotaxin in NL, BAL and serum peaked between 2-12 hours after OVA challenge in ULAI mice, and at 24 hours in UAI mice, related to the timing of maximal responses of marrow EoB-CFU in the respective groups.<p></p> <b>Conclusions</b> Multiple-site antigen challenges cause earlier increases of local and systemic IL-5 and eotaxin, accompanied by earlier up-regulation of marrow responses. These data support the concept that systemic mechanisms linking rhinitis to asthma depend on location and extent of airways allergen exposure.<p></p&gt