Der Effekt von Infliximab auf TNF-α-induzierte Mucin-Sekretion in humanen Atemwegsepithelien

Introduction The burden of chronic obstructive airway diseases increases daily. Among these diseases are chronic obstructive pulmonary disease (COPD), bronchial asthma and cystic fibrosis (CF). Common features are a hypersecretion of airway mucus and an obstruction of the airways with a highly elevated risk of inflammation. Problem Aside from the establishment and optimisation of an ALI cell culture system the main objective of this thesis was to find out whether mucin hypersecretion caused by TNF-α stimulation could be inhibited by Infliximab. Methods Different human airways epithelium cell lines were supplied with varying cell culture media. Furthermore, the cell culture conditions, the preparation of the ALI inserts, the quantity of cell culture medium, the frequency of medium supply, and the retrieval of the samples were optimized. Cells were stimulated with TNF-α, LPS of Pseudomonas aeruginosa, and LT-α, Infliximab was used for inhibition. All samples were submitted to Western blot analysis. Results TNF-α dose- and time-dependently stimulates mucin secretion in human airway epithelium cell lines. This increase in mucin secretion can be inhibited by Infliximab, even in the case of a basal stimulation with TNF-α and apical inhibition with Infliximab. LT-α and LPS of Pseudomonas aeruginosa can also trigger mucin secretion, whereas hypersecretion caused by LT-α can be inhibited by Infliximab, hypersecretion caused by LPS can not. Discussion Topical admission of Infliximab, e.g. as an aerosol, could inhibit inflammation mediated by TNF-α and thereby reduce mucin hypersecretion in chronic obstructive airway diseases without causing the grave adverse effects of systemic admission.