Dissecting the inflammatory twitch in allergically inflamed mice

Abstract

We have previously advanced the hypothesis that the allergic inflammatory response in the lungs occurs as a self-limited sequence of events that begins with the onset of inflammation and then resolves back to baseline over a predetermined time course (Pothen JJ, Poynter ME, Bates JH. J Immunol 190: 3510–3516, 2013). In the present study we tested a key prediction of this hypothesis, which is that the instigation of the allergic inflammatory response should be accompanied by a later refractory period during which the response cannot be reinitiated. We challenged groups of ovalbumin-sensitized BALB/c mice for 3, 14, 21 and 31 consecutive days with aerosolized ovalbumin. We measured airways responsiveness as well as cell counts and cytokines in bronchoalveolar lavage fluid after the final challenge in subgroups from each group. In other subgroups we performed the same measurements following rest periods and after a final single recall challenge with antigen. We determined that the refractory periods for GM-CSF, KC, and IL-5 are no longer than 10 days, while those for IFNγ and IL-10 are no longer than 28 days. The refractory periods for total leukocytes and neutrophils were no greater than 28 days, while that for eosinophils was more than 28 days. The refractory period for airways resistance was less than 17, while for lung elastance it was longer than 28 days. Our results thus demonstrate that the components of the allergic inflammatory response in the lung have finite refractory periods, with the refractory period of the entire response being in the order of a month.