Airway neutrophils and interleukin-17

Abstract

Airway neutrophils and interleukin-17. A. Linde Ân, H. Hoshino, M. Laan. #ERS Journals Ltd 2000. ABSTRACT: It is well known that exacerbations of obstructive airways disease such as asthma and chronic obstructive pulmonary disease are associated with an increased number of neutrophils in the airways. However, the mechanisms behind this phenomenon are poorly understood.There is in vivo experimental evidence that the number of airway neutrophilis is controlled by certain T-lymphocytes, but the mediators responsible for this lymphocyte-related neutrophilia have not yet been identified.In this review, novel evidence that the T-lymphocyte-related cytokine interleukin (IL)-17 can link the activation of certain T-lymphocytes to the recruitment and activation of airway neutrophils is described. The IL-17-induced neutrophil recruitment is mediated via induced CXC chemokine release through steroid-sensitive mechanisms and is modulated by release of endogenous tachykinins. These effects of IL-17 are potentiated by other pro-inflammatory cytokines such as (IL-1b) and tumour necrosis factor-a.Clinical studies are needed to evaluate whether or not targeting these mechanisms can provide a useful pharmacotherapeutical approach against exaggerated mobilization of neutrophils in obstructive airways disease. Eur Respir J 2000; 15: 973±977.

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma

“…This is the first demonstration that a T H 2 cytokine can coordinate with a proinflammatory cytokine, such as IL-17A, to potentiate a T H 2 response. 11,18,[28][29][30][31] This discovery emphasizes the uniqueness of epithelia-derived IL-19 in allergic diseases and suggests important roles for IL-13 and IL-17A in IL-19 regulation. [32][33][34] We hypothesize that airway epithelial IL-19 is induced by IL-17A and T H 2 cytokines, mainly IL-13, to further potentiate a T H 2-dominant response in a positive feedback manner in the context of allergic airway diseases, such as asthma.…”

“…18,28,30,[37][38][39] Studies have found that in patients with moderate-to-severe asthma, neutrophils are found to be more abundant than eosinophils in the bronchoalveolar lavage fluid. 30,31,40 IL-17A can promote neutrophil recruitment, which might contribute to certain asthmatic phenotypes characterized by both high neutrophil counts and IL-17A expression. Other potential roles of IL-17A in asthmatic airways might include the stimulation of mucus cell differentiation 25,41 and induction of chemokine and nitric oxide release.…”

Free, soluble interleukin-17 protein during severe inflammation in human airways

“…Neutrophils are also present and activated in the airways during acute, severe exacerbations of bronchial asthma [1,2]. For these inflammatory airway diseases, there is now evidence that the activated neutrophils may contribute to bronchial hyperresponsiveness, epithelial damage, hypersecretion and tissue remodelling, by releasing proteolytic enzymes and free oxygen radicals [1][2][3][4][5].…”

“…Recent studies on rodents in vivo suggest that the cytokine interleukin (IL)-17 links the activation of certain T-lymphocytes to neutrophil recruitment in the airways [1]. It is possible that IL-17 causes neutrophil recruitment and activation by inducing production of neutrophil-mobilizing cytokines, such as IL-6 and IL-8, released from bronchial epithelial and other airway cells [9][10][11].…”

“…The recruitment and activation of neutrophils in the airways constitutes a hallmark of chronic bronchitis and chronic obstructive pulmonary disease [1]. Neutrophils are also present and activated in the airways during acute, severe exacerbations of bronchial asthma [1,2].…”