We previously reported impaired glucocorticoid-induced production of the anti-inflammatory cytokine IL-10 by CD4+ T cells from glucocorticoid resistant (SR), in comparison to glucocorticoid sensitive (SS), asthma patients. Since SR may be an acquired or inducible defect, we investigated immune manipulations that can restore IL-10 synthesis in these patients and, based on our previous studies of IL-10 synthesizing regulatory T cells, we have used vitamin D3 and pre-treatment with IL-10 for this purpose.

Patient cells were stimulated directly, or following overnight pre-culture in medium or IL-10, with anti-CD3 with or without dexamethasone and vitamin D3 (active form) for 7 days. Cells were then washed and restimulated with anti-CD3 alone and IL-10 synthesis assayed by ELISA and flow cytometry.

Stimulation in the presence of dexamethasone plus vitamin D3, restored IL-10 synthesis in SR cultures to >50% of that noted in SS patient cultures. Furthermore, pre-treatment with IL-10 prior to stimulation in the presence of dexamethasone alone or plus vitamin D3 fully restored IL-10 synthesis.

These data provide evidence for a potential contribution of IL-10 in the clinical efficacy of glucocorticoids and suggest mechanisms to enhance glucocorticoid efficacy in difficult to treat asthma.