Evidence of Dysregulated Cytokine Production by Sinus Lavage and Peripheral Blood Mononuclear Cells in Patients With Treatment-Resistant Chronic Rhinosinusitis | Otolaryngology | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Original Article
December 2001

Evidence of Dysregulated Cytokine Production by Sinus Lavage and Peripheral Blood Mononuclear Cells in Patients With Treatment-Resistant Chronic Rhinosinusitis

Author Affiliations

From the Departments of Pediatrics (Drs Jyonouchi and Sun and Mr Le) and Otolaryngology (Dr Rimell), School of Medicine, University of Minnesota, Minneapolis.

Arch Otolaryngol Head Neck Surg. 2001;127(12):1488-1494. doi:10.1001/archotol.127.12.1488
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-γ] 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-γ, 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-γ production by PBMCs was observed in 6 patients with CRS compared with controls, but 4 of them had elevated IFN-γ 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-γ 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.

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