IL-18 in induced sputum and airway hyperresponsiveness in mild asthmatics: Effect of smoking

Interleukin 18 (IL-18) is a pro-inflammatory cytokine, which has been shown to be implicated in the induction of airway hyperresponsiveness (AHR) in murine asthma models. The association of IL-18 with AHR in human bronchial asthma is not clear as yet. As cigarette smoking modifies airway inflammation we aimed to assess the relationship of IL-18 with airway hyperresponsiveness (AHR) in non-smoking versus smoking asthmatics. IL-18 was measured in sputum supernatants obtained from asthmatic (24 smokers and 22 non-smokers) and healthy subjects (16 smokers and 17 non-smokers). All subjects were assessed by spirometry, skin-prick tests to common aeroallergens and bronchial provocation to methacholine (Mch). There was no significant difference in IL-18 levels between healthy and asthmatic smokers and between healthy and asthmatic non-smokers. IL-18 levels in sputum were significantly lower in healthy smokers compared to non-smokers (p = 0.048); similarly, in asthmatic smokers as compared to non-smokers (p = 0.037). An inverse correlation was found between IL-18 levels, FEV1 (% pred) (r = -0.495, p = 0.043), and PD20MCh in non-smoking asthmatics (r = -0.621, p = 0.024). A positive correlation was found in smoking asthmatics between IL-18 levels in sputum and FEV1 (% pred) (r = 0.627, p = 0.002), FVC (% pred) (r = 0.460, p = 0.031), and PD20MCh (r = 0.809, p = 0.005). Cigarette smoking reduced IL-18 levels in induced sputum in healthy and asthmatic smokers. IL-18 levels were correlated with airway obstruction and AHR in an inverse way in smoking and non-smoking asthmatics. These results suggest the implication of IL-18 in airway hyperresponsiveness characterizing bronchial asthma, which is modified by smoking. (C) 2009 Elsevier Ltd. All rights reserved.