Abstract
William of Ockham (of Ockham's Razor fame) and Albert Einstein both urged us to keep it simple, but biology, perhaps in comparison to philosophy or physics, is often a more complicated matrix. An example of the complex nature of nature is the case of chemokine action in mediating inflammatory disease. Thus, chemokines were associated initially with the development of inflammatory and allergic disease primarily through their role as chemoattractant cytokines. In turn, increased lung levels of the chemokine CCL5 in patients with asthma and in mouse models of asthma (1, 2) were presumed to cause further recruitment of inflammatory cells, especially eosinophils, into airway tissue and consequent worsening of airway disease. However, this view of CCL5, and chemokines in general, turns out to be quite naive, as underscored by an additional article in the current issue of the AJRCMB (3). In this new article, Koya and colleagues (pp 147–154) show that CCL5 selectively dampens the long-term effect of allergen challenge in mice (3). In this model, prolonged allergen exposure (out to 48 d after initial sensitization) led to airway hyperreactivity and mucous cell metaplasia, and administration of CCL5 decreased these traits, whereas treatment with anti-CCL5 antibody significantly increased them. Administration of CCL5 also caused an increase while anti-CCL5 antibody caused a decrease in BAL fluid levels of IFN-γ as well as IFN-γ-producing CD4 T cells. Moreover, anti–IFN-γ antibody treatment caused an increase in airway hyperreactivity. Together, the results suggest that CCL5 somehow stimulates the generation of IFN-γ–producing Th1 cells that protect against a prolonged allergic response. Whether concomitant changes in lung IL-12 levels are linked to this mechanism remains uncertain. Similarly, why this action takes place after longer- but not shorter-term allergen exposure still needs to be defined, but presumably relies on the delayed development of an activated Th1 cell population.
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More From: American Journal of Respiratory Cell and Molecular Biology
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