Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps

Anju T. Peters, Atsushi Kato, Ning Zhang, David B. Conley, Lydia Suh, Brian Tancowny, Derek Carter, Tara Carr, Michael Radtke, Kathryn E. Hulse, Sudarshan Seshadri, Rakesh Chandra, Leslie C. Grammer, Kathleen E. Harris, Robert Kern, Robert P. Schleimer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Background: IL-6 activates TH17 cells and regulates the response of B lymphocytes and regulatory T cells. The IL-6 receptor and the membrane protein, glycoprotein 130 (gp130), form an active signaling complex that signals through signal transducer and activator of transcription 3 (STAT3) and other signaling molecules. Both the IL-6 receptor (IL-6R) and gp130 can be found in soluble forms that regulate the pathway. Objective: We measured IL-6 signaling components and IL-17 in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls to assess the IL-6 pathway in CRS. Methods: IL-6, soluble IL-6R, soluble gp130 (sgp130), and IL-17 were measured in sinus tissue extracts and in nasal lavage fluid by either cytokine bead array or ELISA. phosphoSTAT3 (p-STAT3) was determined by Western blot and by immunohistochemistry. Results: IL-6 protein was significantly (P < .001) increased in CRSwNP compared with CRSsNP and controls. Soluble IL-6R was also increased in nasal polyp compared with control tissue (P < .01). Despite elevated IL-6 and sIL-6R, IL-17A, E, and F were undetectable in the sinus tissue from most of the patients with CRS and controls. p-STAT3 levels were reduced in the polyp tissue, possibly indicating reduced activity of IL-6 in the tissue. sgp130 was elevated in CRSwNP compared with CRSsNP and controls. Conclusion: p-STAT3 levels are decreased in CRSwNP despite increased levels of IL-6 and sIL-6R and are associated with the absence of an IL-17 response. This may be a response to elevated levels of sgp130, a known inhibitor of IL-6 signaling. These results indicate that IL-6 and its signaling pathway may be altered in CRSwNP.

Original languageEnglish (US)
Pages (from-to)397-403.e10
JournalJournal of Allergy and Clinical Immunology
Volume125
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • Chronic rhinosinusitis
  • IL-17
  • IL-6
  • IL-6 receptor
  • nasal polyps
  • phospho-STAT3
  • soluble glycoprotein 130

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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