Interleukin-8 receptor modulates IgE production and B-cell expansion and trafficking in allergen-induced pulmonary inflammation

We examined the role of the interleukin-8 (IL-8) receptor in a murine model of allergen-induced pulmonary inflammation using mice with a targeted dele tion of the murine IL-g receptor homologue (IL-8r(-/-)). Wild-type (Wt) and IL-8r(-/-) mice were systemically immunized to ovalbumin (OVA) and were ex posed with either single or multiple challenge of aerosolized phosphate-buf fered saline (OVA/PBS) or OVA (OVA/OVA). Analysis of cells recovered from b ronchoalveolar lavage (BAL) revealed a diminished recruitment of neutrophil s to the airway lumen after single challenge in IL-8r(-/-) mice compared wi th Wt mice, whereas multiply challenged IL-8r(-/-) mice had increased B cel ls and fewer neutrophils compared with Wt mice. Both Wt and IL-8r(-/-) OVA/ OVA mice recruited similar numbers of eosinophils to the BAL fluid and exhi bited comparable degrees of pulmonary inflammation histologically. Both tot al and OVA-specific IgE levels were greater in multiply challenged IL-8r(-/ -) OVA/OVA mice than in Wt mice. Both the IL-8r(-/-) OVA/OVA and OVA/PBS mi ce were significantly less responsive to methacholine than their respective Wt groups, but both Wt and IL-8r mice showed similar degrees of enhancemen t after multiple allergen challenge. The data demonstrate that the IL-8r mo dulates IgE production, airway responsiveness, and the composition of the c ells (B cells and neutrophils) recruited to the airway lumen in response to antigen.