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Blood cytotoxic/inflammatory mediators in non‐eosinophilic asthma
Author(s) -
Hodge S.,
Hodge G.,
Simpson J. L.,
Yang I. A.,
Upham J.,
James A.,
Gibson P. G.,
Reynolds P.N.
Publication year - 2016
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12634
Subject(s) - immunology , granzyme b , granzyme a , cytotoxic t cell , granzyme , natural killer t cell , perforin , medicine , cd8 , interleukin 21 , immune system , biology , in vitro , biochemistry
Summary Background Non‐eosinophilic asthma ( NEA ) is a distinct, often corticosteroid‐resistant inflammatory asthma phenotype. NK and NKT ‐like cells are effector lymphocytes that we have shown, like CD 28null T cells, to be relatively resistant to steroids and major sources of pro‐inflammatory/cytotoxic mediators. We hypothesized that these cells and mediators would be increased in peripheral blood in NEA . Methods Adults with severe asthma and variable airflow obstruction, poorly controlled despite maintenance therapy with inhaled glucocorticosteroids and long‐acting bronchodilators, were recruited. Blood was assessed in those with eosinophilic asthma ( n = 12), NEA ( n = 25) and healthy non‐smoking controls ( n = 30). We applied flow cytometry to measure T, CD 28null, NK and NKT ‐like cells and their expression of granzyme B, perforin, and killer inhibitory/activating receptors CD 94(Kp43), CD 158b and CD 107A. Intracellular pro‐inflammatory cytokine production ( IFN ‐γ and TNF ‐α) was assessed in 18 controls and 10 patients with asthma/group. Results In NEA , there was increased expression of granzyme B by CD 8+ T cells vs. controls. There was increased expression of granzyme B and CD 158 and decreased CD 94 on NK cells, vs. healthy controls and those with eosinophilic asthma. IFN ‐γ production by NK cells and TNF ‐α production by NKT ‐like cells in NEA were significantly increased vs. controls. In both eosinophilic and NEA phenotypes, there were significant increases in CD 4+28null T cells (72% and 81% increases, respectively, vs. controls) and their expression of pro‐inflammatory cytokines. Significant correlations were noted between blood CD 4+28null T cells and neutrophil numbers in induced sputum, and between corticosteroid dose and blood NKT ‐like cells, and their production of granzyme B and TNF ‐α and NK IFN ‐γ. Conclusion and clinical relevance In poorly controlled asthma, altered expression of cytotoxic/pro‐inflammatory mediators can be seen on a variety of lymphocyte subsets in the peripheral blood; these changes are most apparent in NEA . Whether this pattern of expression is a marker of treatment responsiveness and future risk of exacerbations remains to be determined.