title: Th2-type cytokines modulate IL-6 release by human bronchial epithelial cells.
abstract: The multifunctional cytokine IL-6, which can be locally produced by human bronchial epithelial cells (HBECs), has been found to play a role in IL-4 dependent IgE synthesis. Since the allergic reaction in bronchial asthma is associated with the upregulation of IL-4 and Th2 type of immune response, the purpose of our study was to assess whether IL-4 and related cytokines IL-10 and IL-13 regulate IL-6 release by HBEC s. HBECs were obtained by bronchial brushing, cultured in LHC-9/RPMI 1640. At the third passage the cells were stimulated with cytokines (0.1-20 ng/ml) diluted in unsupplemented media for 24 h. The supernatants were tested for IL-6 content by sandwich ELISA. Unstimulated HBECs produced detectable amounts of IL-6 (368+/-25 pg/ml). Exposure to IL-10 (368+/-22 pg/ml) and IL-13 (395+/-6 pg/ml) resulted in little changes. IL-4 caused a slight but significant increase in IL-6 release (530+/-45 pg/ml), P<0.05, TNFalpha (1657+/-85 pg/ml) and IFNgamma (1953+/-37 pg/ml) showed strong induction of IL-6 release in HBECs (P<0.005 and P<0.001, respectively). Both IL-4 and IL-13 significantly inhibited TNF induced IL-6 release (P<0.01 for both) while augmenting the effect of IFNgamma (P<0.005 and P<0.01, respectively.). IL-10 was without a significant effect. We conclude that Th2-type cytokines IL-4 and IL-13 affect the release of IL-6 by HBECs in response to TNFalpha (inhibition) and IFgamma (augmentation). IL-10 had no effect on the regulation of IL-6 release. Modulation of IL-6 levels by Th2-type cytokines may play a role in allergic reactions through the IL-6 promoting effect on IL-4 mediated IgE production.
authors.affiliation: Department of Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. striz@mbox.cesnet.cz
authors.forename: I
authors.initials: I
authors.lastname: Stríz
authors.forename: T
authors.initials: T
authors.lastname: Mio
authors.forename: Y
authors.initials: Y
authors.lastname: Adachi
authors.forename: D J
authors.initials: DJ
authors.lastname: Romberger
authors.forename: S I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016895:Culture Media, Serum-Free; D018793:Interleukin-13; D015850:Interleukin-6; D015847:Interleukin-4