IP-10 mediated reinforcement of human type 1 cytokine synthesis to environmental allergens among non-atopic subjects

Background: Non-atopic subjects do not differ from those with allergic rhinitis or asthma in their ability to respond to environmental antigens, but in the nature of their response. IP-10, a CXC (cc) chemokine, is produced by a wide variety of cell types, and differs from most chemokines in its specificity for activated lymphocytes. Here, we examine its potential role in the maintenance of putatively protective, type-1-dominated cytokine responses among non-atopic individuals. Methods: The impact of rIP-10 on polyclonally driven, grass-pollen-and catantigen-stimulated type 1 (IFN gamma) and type 2 (IL-4) cytokine responses was examined in short-term cultures of fresh PBMC from non-atopic subjects directly ex vivo. Results: rIP-10 selectively enhanced polyclonally driven and antigen-specific IFN gamma, but not IL-4, responses, with median increases ranging from 100 to 400% following polyclonal activation and 20 to 30-fold in antigen-driven IFN gamma responses. rIP-10 levels with maximal activity were at or below those previously reported for maximal chemotactic activity and, most importantly, were within the range of those seen in plasma obtained from non-atopic subjects during the grass pollen season. Conclusions: The data suggest a potential role for IP-10 in the maintenance of protective, type-l-dominated responses in non-atopic subjects. They raise the possibility that this chemokine could be of therapeutic value in individuals with established type-2-dominated responses, e.g. in patients with immediate hypersensitivity.