Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps.
BACKGROUND
IL-6 activates T(H)17 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.


CONCLUSIONS
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.
Division of Allergy-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Anju T
AT
Peters
Atsushi
A
Kato
Ning
N
Zhang
David B
DB
Conley
Lydia
L
Suh
Brian
B
Tancowny
Derek
D
Carter
Tara
T
Carr
Michael
M
Radtke
Kathryn E
KE
Hulse
Sudarshan
S
Seshadri
Rakesh
R
Chandra
Leslie C
LC
Grammer
Kathleen E
KE
Harris
Robert
R
Kern
Robert P
RP
Schleimer
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002908:Chronic Disease; D050822:Cytokine Receptor gp130 / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000276:immunology* / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000276:immunology / Q000378:metabolism; D012220:Rhinitis / Q000276:immunology* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
D020381:Interleukin-17; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050822:Cytokine Receptor gp130