SELECTED ARTICLES FROM THE RECENT LITERATURE 2008

8/15/2008

More missing pieces in the puzzle of anti-IL-5 and eosinophilia

Summary
These two articles, published back-to-back in the same issue of The Journal of Allergy and Clinical Immunology deal with eosinophilia and factors which affect eosinophil levels, and the effect of anti-IL-5, mepolizumab, on eosinophils and eosinophilic diseases.

The first article,by Stein, et al., looked at the effect of anti-IL-5 infusions in 25 patients with a variety of eosinophilic disorders. As seen in previous investigations, the majority of these patients (23) responded to therapy with anti-IL-5. Symptom levels fell significantly in these patients, and the fall persisted for three months after the final infusion in 76% of those responding. Of note is that they also found that this fall was associated with a large increase in blood IL-5 levels, probably because of anti-IL-5/mepolizumab complexes.

In addition, possibly because of a compensatory response, they noted an increase in eosinophil IL-5 receptor alpha expression as well as an increase of CD4 positive and CD8 positive cells producing intracellular IL-5. This suggested to them that anti-IL-5 therapy activated an endogenous IL-5 autoregulatory pathway.

The second article, Cherry, et al., found that IL-33, a member of the IL-1 cytokine family, can induce eosinophil superoxide anion production and eosinophil degranulation as potently as does IL-5. IL-33 also increased eosinophil survival and induced production of IL-8. These effects were inhibited by an antibody to the IL-33 receptor, ST2.

Of importance is that the expression pattern of human IL-33 appears limited to epithelial cells from the bronchus and small airways, as well as fibroblast and smooth muscle cells. This of course suggests that this cytokine is active in regulating mucosal eosinophilic responses in the lung.

These observations by Cherry, et al., suggest that one of the reasons anti-IL-5 is active in systemic eosinophilic disorders (as described by Stein, et al.), yet has failed to demonstrate effectiveness in asthma (although peripheral blood eosinophil levels decline) might be the effect of IL-33, which could be limited to the lung.

Reference

1. Stein ML, et al. Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. Journal of Allergy and Clinical Immunology 2008; 121(6):1473-1483.

2. Cherry WB, et al. A novel IL-1 family cytokine, IL-33, potently activates human eosinophils. Journal of Allergy and Clinical Immunology 2008; 121(6):1484-1490.

 

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