Endogenous interleukin-10 suppresses allergen-induced airway inflammation and nonspecific airway responsiveness

Background The airway inflammation observed in asthma is orchestrated by ac tivated Th-2 lymphocytes relevant for the induction of altered airway respo nsiveness. An increasing body of evidence is accumulating that not only the pro-inflammatory cytokines interleukin (IL)-4 and IL-5 but also the immuno modulating cytokines IL-12 and possibly IL-10 are crucial for regulating th e allergic airway inflammation. Objective Since IL-10 is capable of downregulating a broad spectrum of pro- inflammatory cytokines, we wanted to address the role of endogenously produ ced IL-10 in vivo in allergic asthma. Methods Knockout (IL-10(-/-)) mice (C57BL/6-IL10tm1Cgn) and wild-type (WT) counterparts were immunized (day 0) and exposed (day 14-21) to ovalbumin (O VA). Airway inflammation and reactivity (AR), serum allergen-specific IgE r esponses and cytokine profiles in the bronchoalveolar lavage fluid (BALF) w ere studied. Results The IL-10(-/-) mice had more eosinophilic airway inflammation but c omparable levels of allergen-specific serum IgE compared to the WT mice aft er allergen challenge. The AR was comparably increased in the OVA challenge d WT and IL-10(-/-) mice vs sham-exposed WT, but not vs sham-exposed IL-10( -/-) mice since these showed a higher baseline AR. IFN gamma, IL-4 and IL-1 3 were comparable and IL-5 was even lower in the BALF of the in IL-10(-/-) mice compared to the similarly exposed WT mice. Conclusion These results indicate that IL-10 plays an important and possibl y direct role in the control of airway inflammation and responsiveness in a n in vivo mouse model of allergy.