Blood cytotoxic/inflammatory mediators in non-eosinophilic asthma

Hodge, S., Hodge, G., Simpson, J. L., Yang, I. A., Upham, J., James, A., Gibson, P. G. and Reynolds, P. N. (2016) Blood cytotoxic/inflammatory mediators in non-eosinophilic asthma. Clinical and Experimental Allergy, 46 1: 60-70. doi:10.1111/cea.12634

Author Hodge, S.
Hodge, G.
Simpson, J. L.
Yang, I. A.
Upham, J.
James, A.
Gibson, P. G.
Reynolds, P. N.
Title Blood cytotoxic/inflammatory mediators in non-eosinophilic asthma
Journal name Clinical and Experimental Allergy   Check publisher's open access policy
ISSN 1365-2222
Publication date 2016-01-01
Year available 2016
Sub-type Article (original research)
DOI 10.1111/cea.12634
Open Access Status Not Open Access
Volume 46
Issue 1
Start page 60
End page 70
Total pages 11
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
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-α) 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.
Keyword Blood
CD4+28null T cells
NK and NKT-like cells
Non-eosinophilic asthma
Pro-inflammatory cytokines
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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