Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients

Els Truyen ¹, Liesbeth Coteur ¹, Ellen Dilissen ¹, Lut Overbergh ¹, Lieven J Dupont ¹, Jan L Ceuppens ¹ and Dominique MA Bullens ^1*

¹ KULeuven, Belgium

^* To whom correspondence should be addressed. E-mail: dominique.bullens{at}med.kuleuven.be.

Accepted 3 January 2006

Abstract

Background: Asthma is a chronic inflammatory disorder of the airways driven by T cell activation. Th2 cells and their cytokines are thought to play a role in the pathophysiology of allergic as well as non-allergic asthma.

Methods: We obtained airway cells by sputum induction in healthy (n=15) and asthmatic (n=39) individuals and studied airway T cell cytokine profiles (Interleukin (IL)-4, IL-5, IL-13, IL-10 and IFN-) at the mRNA level by real-time RT-PCR.

Results: Asthma patients had increased expression of IL-5 (p=0.001) and IL-13 (p=0.03) mRNA in sputum compared to the non asthmatic controls. IL-4 mRNA and IFN- mRNA were detectable in sputum of respectively 44% and 21% of patients but never in controls. Sputum IL-10 mRNA levels did not significantly differ between patients and controls. Sputum mRNA expression levels of IL-4, IL-5 and IL-13 significantly correlated with eosinophil percentages, and were higher in allergic asthmatics than in non-allergics (p=0.03, p=0.02 and p=0.0001 respectively), while they did not differ between mild and moderate-to-severe asthmatics. In contrast, the IFN- mRNA expression was higher in non-allergic than in allergic patients (p=0.04) and higher in the moderate-to-severe asthma patient group than in mild asthmatics (p<0.01). The sputum IL-5 mRNA levels (but not the other cytokine mRNA levels) also correlated with exhaled nitric oxide (eNO) and with bronchial hyperreactivity expressed as the histamine dose resulting in a 20% decrease in FEV1.

Conclusion: Real-time RT-PCR analysis of mRNA in induced sputum confirms a predominance of Th2 cytokines in both allergic and non-allergic asthma. IL-5 reflects eosinophil infiltration as well as eNO levels and hyperreactivity, The Th1 cytokine, IFN- rather points to asthma severity. The technique is a promising tool in further studies on asthma severity and disease activity.

Keywords: Induced sputum, Th1, Th2, asthma, atopy

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