Vitamin D enhances production of soluble ST2, inhibiting the action of IL-33

Paul E Pfeffer,Yin-Huai Chen,Grzegorz Woszczek,Nick C Matthews,Elfy Chevretton,Atul Gupta,Sejal Saglani,Andrew Bush,Chris Corrigan,David J Cousins,Catherine M Hawrylowicz

doi:10.1016/j.jaci.2014.09.044

Abstract

Vitamin D enhances production of soluble ST2, inhibiting the action of IL-33

Highlights

In our cohort of patients with severe asthma, the majority receiving very high doses of inhaled or systemic corticosteroids, a blood eosinophil count of greater than 0.45 3 109 cells/L can correctly predict sputum eosinophilia in 9 of 10 cases
As demonstrated both here and in the article from the Severe Asthma Research Program group,[4] this cutoff would include many patients who do not have contemporaneous sputum eosinophilia and potentially would not be in the group of patients who could benefit from treatment
The consequence of this in a trial of a biologic agent is that the magnitude of benefit could be underestimated or even missed, as happened previously when mepolizumab was trialed in unselected patients.[9]

Summary

METHODS

Ultrahigh-purity 1,25(OH)D3 and 25(OH)D3 (Enzo Life Sciences, Exeter, United Kingdom) were placed in aliquots dissolved in dimethyl sulfoxide (Sigma-Aldrich, Gillingham, United Kingdom). Recombinant proteins were obtained as follows: IL-33, IFN-g, IL-4, human sST2-Fc chimera, and isotype were all from R&D System (Abingdon, United Kingdom)

Primary human epithelial cell culture

Peripheral blood lymphocyte culture

Peripheral blood eosinophil culture

Findings

Statistical analysis