Increased interleukin-13 mRNA expression in bronchoalveolar lavage cells of atopic patients with mild asthma after repeated low-dose allergen provocations

Immune and inflammatory responses mediated by cytokines are essential in th e pathophysiology of asthma. The aim of this study was to analyse the cytok ine mRNA profiles in bronchoalveolar lavage (BAL) cells of patients with mi ld atopic asthma, before and after induction of a subclinical allergic airw ay inflammation. For this purpose, eight patients with mild atopic asthma r eceived low-dose allergen inhalations equivalent to 10% of a provocational dose causing a 20% fall in forced expiratory flow in 1 sec (PD20) for 7 wee kdays. BAL was performed before and after low-dose provocations in patients , and without provocation in five healthy controls. Alveolar macrophages (A M) were enriched by negative selection, using magnetic beads, to enable sep arate studies of the BAL cells. Using a semiquantitative RT-PCR technique, the mRNA expression of macrophage-derived cytokines interleukin (IL)-1, IL- 6, IL-8, IL-10, IL-12, IL-13, interferon (IFN)-gamma, tumour necrosis facto r (TNF)-alpha and transforming growth factor (TGF)-beta was analysed. After low-dose provocations, we observed a significant increase in the expressio n of IL-13 mRNA (P = 0.01) in BAL cells enriched for AM of the asthmatic pa tients. The increased IL-13 mRNA positively correlated with the proportion of BAL fluid eosinophils (r = 0.7, P = 0.05). Moreover, a tendency was foun d towards an increased IL-1 and a reduced IL-6, IL-8, IFN-gamma and TNF-alp ha expression by the BAL cells. Comparing asthmatic patients before low-dos e provocations and healthy controls, a significantly higher expression of I L-6 (P < 0.003), IL-10 (P < 0.005) and TGF-beta (P <0.003) and a significan tly lower expression of IL-8 (P < 0.005) and TNF-alpha (P < 0.01) was detec ted in the patients. In summary, repeated low-dose allergen provocations of asthmatic patients results in a modified BAL cell cytokine mRNA profile wi th increased production of IL-13, that may be of importance for the develop ment of a Th-2-like immune response. A possible source of the increased IL- 13 mRNA is AM, which may have a more active function in the allergic inflam mation than previously thought.