- Title
- Blood cytotoxic/inflammatory mediators in non-eosinophilic asthma
- Creator
- Hodge, S.; Hodge, G.; Simpson, J. L.; Yang, I. A.; Upham, J.; James, A.; Gibson, P. G.; Reynolds, P. N.
- Relation
- NHMRC
- Relation
- Clinical and Experimental Allergy Vol. 46, Issue 1, p. 60-70
- Publisher Link
- http://dx.doi.org/10.1111/cea.12634
- Publisher
- Wiley-Blackwell
- Resource Type
- journal article
- Date
- 2016
- Description
- 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 CD28null 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, CD28null, NK and NKT-like cells and their expression of granzyme B, perforin, and killer inhibitory/activating receptors CD94(Kp43), CD158b and CD107A. Intracellular pro-inflammatory cytokine production (IFN-γ and TNF-a) was assessed in 18 controls and 10 patients with asthma/group. Results: In NEA, there was increased expression of granzyme B by CD8+ T cells vs. controls. There was increased expression of granzyme B and CD158 and decreased CD94 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 CD4+28null T cells (72% and 81% increases, respectively, vs. controls) and their expression of pro-inflammatory cytokines. Significant correlations were noted between blood CD4+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.
- Subject
- blood; CD4+28null T cells; cytotoxic; NK and NKT-like cells; non-eosinophilic asthma; pro-inflammatory cytokines
- Identifier
- http://hdl.handle.net/1959.13/1321486
- Identifier
- uon:24375
- Identifier
- ISSN:0954-7894
- Language
- eng
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