title: Evidence of dysregulated cytokine production by sinus lavage and peripheral blood mononuclear cells in patients with treatment-resistant chronic rhinosinusitis.
abstract: BACKGROUND
  Treatment-resistant chronic rhinosinusitis (CRS) imposes a clinical challenge. Its pathogenesis may be associated with dysregulated immune/inflammatory responses in the sinus.
  
  
  OBJECTIVE
  To evaluate production of types 1 and 2 T cytokines (interferon gamma [IFN-gamma] and interleukin [IL] 5/IL-4, respectively) and regulatory/inflammatory cytokines (IL-10, IL-12, and IL-18) by sinus lavage (SL) cells and peripheral blood mononuclear cells (PBMCs) in patients with treatment-resistant CRS.
  
  
  METHODS
  Sample SL cells and PBMCs obtained from 19 patients with treatment-resistant CRS were cultured with or without stimuli, and cytokine levels in the supernatant were measured using enzyme-linked immunosorbent assay. Control PBMC samples were obtained from 26 children.
  
  
  RESULTS
  Chronic otitis media was found in 15 patients. Neutrophils and/or epithelial cells were dominant in SL cells. IFN-gamma, IL-12p40, and IL-10 (>100 pg/mL) were detected in SL cell cultures from 12, 9, and 8 patients, respectively. Production of IL-12p40 and IL-18 by SL cells correlated positively with phytohemagglutinin and IL-12p70 stimuli. In 12 patients, we detected IL-18 (>100 pg/mL) in SL cell cultures without stimuli, whereas PBMCs produced little IL-18, irrespective of stimuli. There was no correlation between cytokine levels produced by SL cells and PBMCs, except for IL-12p40 produced using IL-18. Decreased IFN-gamma production by PBMCs was observed in 6 patients with CRS compared with controls, but 4 of them had elevated IFN-gamma production by SL cells. Production of IL-12p40 by PBMCs was higher in 10 patients with CRS than in controls, and 7 of these patients had lower IL-10 production, resulting in an increased IL-12p40/IL-10 ratio.
  
  
  CONCLUSIONS
  There is a role for locally produced regulatory cytokines in IFN-gamma production in the sinus in patients with treatment-resistant CRS. However, aberrant cytokine production patterns by PBMCs can be detected at high frequency in these patients, indicating that this can be used as a prognostic marker for patients with CRS.
authors.affiliation: Department of Pediatrics, School of Medicine, University of Minnesota, MMC 610 FUMC, 420 Delaware St SE, Minneapolis, MN 55455, USA. jyono001@tc.umn.edu
authors.forename: H
authors.initials: H
authors.lastname: Jyonouchi
authors.forename: S
authors.initials: S
authors.lastname: Sun
authors.forename: H
authors.initials: H
authors.lastname: Le
authors.forename: F L
authors.initials: FL
authors.lastname: Rimell
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear; D008297:Male; D017817:Nasal Lavage Fluid / Q000166:cytology / Q000276:immunology*; D012220:Rhinitis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D012852:Sinusitis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D007378:Interleukins; D007371:Interferon-gamma