Abstract
Rationale: Natural killer (NK) cells function is regulated by multiple cell-surface receptors. Nowadays little is known about the involvement and function of NK cells in COPD. Recently a role in pulmonary immunity has been ascribed to NK cells and several in vitro studies have shown corticosteroid-induced inhibition of NK cell-mediated cytotoxicity.
Methods: NK cells were isolated from peripheral blood of healthy volunteers and COPD patients. Cells were cultured for 20 hours in 96-well plates with IL-2 (100 I.U./ml)+IL-12 (2,5 ng/ml), in the absence or in the presence of budesonide (B) (1μM and 10nM) and formoterol (F) (30 and 0,3nM) alone or in combination. Cells were analyzed by flow cytometry and supernatants were used to investigate the production of IFN-γ by ELISA technique.
Results: We found no difference in expression of NK cell receptors analyzed in resting conditions both in healthy volunteers and patients. When cells were stimulated over night with cytokines and treated with drugs, only NKG2D receptor resulted modulated. Its expression was significantly reduced by budesonide alone and in combination, irrespectively of the dose, in COPD patients (p<0.05 and p<0.01, respectively). IFN-γ production induced by stimulation with IL2+IL12 was higher in healthy volunteers than in patients (p<0.05), but it was decreased in a highly significant way (p<0.01) by all treatments in both groups.
Conclusion: Our results show that NKG2D expression and IFN-γ secretion are modulated by treatment with budesonide, both alone and in combination with formoterol, in COPD patients. This might be of relevance in the treatment of diseases such as COPD.
This work was supported by ARMIA and AstraZeneca.
- © 2011 ERS