title: Failure of itraconazole to prevent T-helper type 2 cell immune deviation: Implications for chronic rhinosinusitis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics and Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: John W
authors.initials: JW
authors.lastname: Steinke
authors.forename: Lixia
authors.initials: L
authors.lastname: Liu
authors.forename: Julie
authors.initials: J
authors.lastname: Negri
authors.forename: Larry
authors.initials: L
authors.lastname: Borish
authors.forename: Spencer C
authors.initials: SC
authors.lastname: Payne
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D017964:Itraconazole / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012220:Rhinitis / Q000188:drug therapy*; D012852:Sinusitis / Q000188:drug therapy*; D058408:Th1-Th2 Balance / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D017964:Itraconazole