Raised interferon beta, type 3 interferon and interferon stimulated genes - evidence of innate immune activation in neutrophilic asthma.
; Hilzendeger, Clarissa ; et al
in Clinical & Experimental Allergy : Journal of the British Society for Allergy & Clinical Immunology (2016)
BACKGROUND: Interferons play an important role in innate immunity. Previous studies report deficiency in virus-induction of interferon (IFN)-alpha, -beta and -lambda in bronchial epithelial and bronchial ... [more ▼]
BACKGROUND: Interferons play an important role in innate immunity. Previous studies report deficiency in virus-induction of interferon (IFN)-alpha, -beta and -lambda in bronchial epithelial and bronchial lavage cells in atopic asthmatics. It is now recognized that asthma is a heterogeneous disease comprising different inflammatory phenotypes, some of which may involve innate immune activation in the absence of overt infection. OBJECTIVE: The aim of the study was investigate if the severity of asthma or a specific cellular sputum pattern may be linked to evidence of innate immune activation. METHODS: Here we investigate the expression of IFN-beta, IFN-lambda1 (IL-29), IFN-lambda2/3 (IL-28A/B) and the interferon-stimulated genes (ISGs) myxovirus resistance 1 (Mx1), oligoadenylate synthetase (OAS) and viperin in unstimulated sputum cells in 57 asthmatics (including 16 mild, 19 moderate and 22 severe asthma patients) and compared them with 19 healthy subjects. RESULTS: We observed increased expression of IFN-beta, IFN-lambda1/IL-29, OAS and viperin in asthmatic compared to healthy subjects while IL-28 was not expressed in any group. The overexpression was restricted to neutrophilic asthmatics (sputum neutrophils >/= 76%) while eosinophilic asthmatics (sputum eosinophils >/= 3%) did not differ from healthy subjects or even showed a lower expression of Mx1. No difference in interferon or ISG expression was seen according to clinical asthma severity. CONCLUSION AND CLINICAL RELEVANCE: Neutrophilic, but not eosinophilic, asthmatics display overexpression of IFN-beta, IFN-lambda1/IL-29 and ISGs in their sputum cells that may reflect ongoing innate immune activation. This article is protected by copyright. All rights reserved. [less ▲]Detailed reference viewed: 19 (4 ULg)
Disturbed Cytokine Production at the Systemic Level in Difficult-to-Control Atopic Asthma: Evidence for Raised Interleukin-4 and Decreased Interferon-gamma Release following Lipopolysaccharide Stimulation.
MANISE, Maïté ; SCHLEICH, FLorence ; QUAEDVLIEG, Valérie et al
in International Archives of Allergy & Immunology (2012), 158(1), 1-8
Background: Disturbed cytokine production is thought to govern inflammation in asthma, which, in its turn, may lead to uncontrolled disease. The aim of this study was to assess the relationship between ... [more ▼]
Background: Disturbed cytokine production is thought to govern inflammation in asthma, which, in its turn, may lead to uncontrolled disease. The aim of this study was to assess the relationship between cytokine production from blood leucocytes and the level of asthma control. Methods: We compared the production of interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-gamma and tumour necrosis factor-alpha from peripheral blood leucocytes in non-atopic healthy subjects (n = 22), atopic non-asthmatics (n = 10), well-controlled asthmatics [Juniper asthma control questionnaire (ACQ) score <1.5; n = 20] and patients with uncontrolled asthma despite inhaled or oral corticoids (ACQ score >/=1.5; n = 20). Fifty microlitres of peripheral blood was incubated for 24 h with RPMIc, lipopolysaccharide (LPS; 1 ng/ml) or phytohaemagglutinin (1 mug/ml), and cytokines were measured by immunotrapping (ELISA). Results: Both controlled and uncontrolled asthmatics as well as atopic non-asthmatics spontaneously produced more IL-4 than non-atopic healthy subjects (p < 0.001). IL-4 production induced by LPS was significantly greater (p < 0.05) in both asthma groups compared to atopic non-asthmatics and non-atopic healthy subjects. By contrast, IFN-gamma release induced by LPS was lower in uncontrolled asthmatics than in non-atopic healthy subjects (p < 0.05) and controlled asthmatics (p < 0.05). IL-10 release after LPS was greater in uncontrolled asthmatics than in atopic non-asthmatics (p < 0.05). No difference was observed regarding other cytokines. Conclusion: Blood cells from patients with difficult-to-control atopic asthma display highly skewed Th2 cytokine release following LPS stimulation. [less ▲]Detailed reference viewed: 60 (11 ULg)