title: IL-1 family members IL-18 and IL-33 upregulate the inflammatory potential of differentiated human Th1 and Th2 cultures.
abstract: The IL-1 family members IL-1β, IL-18, and IL-33 are potent cytokines in relationship to amplifying the CD4(+) T cell cytokine production. To evaluate their impact on in vitro-differentiated human Th1 and Th2 cultures, such cultures were established from naive T cells, purified from healthy blood donors, and reactivated in the presence of IL-1β, IL-18, or IL-33. Interestingly, we observe modifying responses in Th1 and Th2 cultures induced by IL-18 or IL-33 but not by IL-1β, both contributing to amplify production of IL-5, IL-13, and IFN-γ. IL-18 or IL-33 stimulation of Th1 cultures resulted in increased IFN-γ and IL-13 production concurrent with reduced IL-10 gene transcription and secretion even though Th1 cultures, in contrast to IL-18Rα, had low ST2L expression. Furthermore, adding IL-18 to Th1 cultures promoted Tbet mRNA expression and production. Th2 cultures stimulated with IL-18 or IL-33 had an increased IL-5 secretion. Interestingly, E4BP4 gene expression and the percentage of E4BP4(+) cells of the recently shown IL-10 transcriptional regulator E4BP4 correlated with IL-10 gene expression and protein secretion in Th1 cultures. Taken together, we report that the IL-1 family "alarmins" IL-18 and IL-33 in addition to amplifying both Th1- and Th2-associated cytokines block production of the regulatory cytokine IL-10 in Th1 cultures.
authors.affiliation: Laboratory of Medical Allergology, Allergy Clinic, Copenhagen University Hospital at Gentofte, 2900 Hellerup, Denmark. lars.blom@regionh.dk
authors.forename: Lars
authors.initials: L
authors.lastname: Blom
authors.forename: Lars K
authors.initials: LK
authors.lastname: Poulsen
mesh_terms: D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000502:physiology*; D000067596:Interleukin-33; D007378:Interleukins / Q000502:physiology*; D005810:Multigene Family / Q000276:immunology; D013489:Suppression, Genetic; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; C506536:IL33 protein, human; D020382:Interleukin-18; D000067596:Interleukin-33; D007378:Interleukins; D016753:Interleukin-10