Failure of Itraconazole to Prevent T-Helper Type 2 Cell Immune Deviation: Implications for Chronic Rhinosinusitis. Issue 6 (September 2016)

• Record Type: Journal Article
• Authors: Kennedy, Joshua L.; Steinke, John W.; Liu, Lixia; Negri, Julie; Borish, Larry; Payne, Spencer C.
• Is Part Of: American journal of rhinology & allergy. Volume 30:Issue 6(2016)
• Page Start: 379
• Page End: 384
• Publication Date: 2016-09
• Subjects: Nose -- Periodicals; Allergy -- Periodicals; 616.21005
• DOI: 10.2500/ajra.2016.30.4362
• Languages: English
• ISSNs: 1945-8924

Abstract

Background: T-helper (Th) type 2 cell inflammation is the hallmark of several disease processes, including asthma, atopic dermatitis, and some forms of chronic rhinosinusitis. Itraconazole has been used as both an antifungal and an anti-inflammatory agent, with some success in many of these diseases, in part, by altering Th2 cytokine expression by T cells. It is not known whether this merely reflects inhibition of established Th2-like cells or the inhibition of differentiation of naive T cells into Th2-like cells. Objective: To evaluate the role of itraconazole in the differentiation of naive T cells during activation. Methods: Naive CD45RA + T cells were isolated from peripheral blood mononuclear cells from healthy volunteers. Th1 and Th2 type cells were differentiated in the presence of varying concentrations of itraconazole. After stimulation with anti-CD3 and anti-CD28 beads, carboxyfluorescein succinimidyl ester dilution was performed to evaluate proliferation and intracellular cytokine staining for interleukin (IL) 4 and interferon (IFN) gamma within proliferating T cells was measured along with enzyme-linked immunosorbent assay for secreted IL-5, IL-13, and IFN gamma. Results: Itraconazole had no effect on proliferation of unbiased, Th1, or Th2 cells. Similarly, there was no effect of itraconazole on either intracellular cytokine staining of IL-4 and IFN gamma or secreted cytokine expression of IFN gamma, IL-5, and IL-13 in any of the cell populations. Conclusion: Itraconazole did not alter the ability of naive T cells to proliferate or secrete cytokines under Th1 or Th2 deviating conditions in vitro. As such, reported inhibition of Th2-like lymphocyte function by itraconazole reflected action on mature effector cells and may have underscored why antifungal treatment failed in many clinical trials of eosinophilic chronic rhinosinusitis.