Cytokines in chronic rhinosinusitis role in eosinophilia and aspirin-exacerbated respiratory disease

Whitney W. Stevens, Christopher J. Ocampo, Sergejs Berdnikovs, Masafumi Sakashita, Mahboobeh Mahdavinia, Lydia Suh, Tetsuji Takabayashi, James E. Norton, Kathryn E. Hulse, David B. Conley, Rakesh K. Chandra, Bruce K. Tan, Anju T. Peters, Leslie C. Grammer, Atsushi Kato, Kathleen E. Harris, Roderick G. Carter, Shigeharu Fujieda, Robert C. Kern, Robert P. Schleimer*

*Corresponding author for this work

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Rationale: The mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD) are not clear. Objectives: To first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and then to investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within nasal polyp (NP) tissues. Methods: Expression levels of numerous inflammatory mediators were determined by quantitative real-time polymerase chain reaction, ELISA, and multiplex immunoassay. Measurements and Main Results: CRSwNP NP had increased levels of type 2 mediators, including IL-5 (P<0.001), IL-13 (P<0.001), eotaxin-2 (P <0.001), and monocyte chemoattractant protein (MCP)-4 (P<0.01), compared with sinonasal tissue from subjects with CRSsNP and control subjects. Expression of IFN-γ messenger RNA or protein was low and not different among the chronic rhinosinusitis subtypes examined. Compared with CRSwNP, AERD NP had elevated protein levels of eosinophil cationic protein (ECP) (P< 0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (P< 0.01), and MCP-1 (P = 0.01), as well as decreased gene expression of tissue plasminogen activator (tPA) (P = 0.02). Despite the higher eosinophilia in AERD, there was no associated increase in type 2 mediator protein levels observed. Conclusions: CRSwNP was characterized by a predominant type 2 inflammatory environment, whereas CRSsNP did not reflect a classic type 1 milieu, as has been suggested previously. AERD can be distinguished from CRSwNP by elevated ECP levels, but this enhanced eosinophilia is not associated with elevations in traditional type 2 inflammatory mediators associated with eosinophil proliferation and recruitment. However, other factors, including GM-CSF, MCP-1, and tPA, may be important contributors to AERD pathogenesis.

Original languageEnglish (US)
Pages (from-to)682-694
Number of pages13
JournalAmerican journal of respiratory and critical care medicine
Volume192
Issue number6
DOIs
StatePublished - Sep 15 2015

Fingerprint

Nasal Polyps
Eosinophilia
Aspirin
Cytokines
Eosinophil Cationic Protein
Chemokine CCL2
Tissue Plasminogen Activator
Granulocyte-Macrophage Colony-Stimulating Factor
Chemokine CCL24
Monocyte Chemoattractant Proteins
Proteins
Interleukin-13
Interleukin-5
Immunoassay
Eosinophils

Keywords

  • CRSsNP
  • CRSwNP
  • Eosinophil

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Stevens, Whitney W. ; Ocampo, Christopher J. ; Berdnikovs, Sergejs ; Sakashita, Masafumi ; Mahdavinia, Mahboobeh ; Suh, Lydia ; Takabayashi, Tetsuji ; Norton, James E. ; Hulse, Kathryn E. ; Conley, David B. ; Chandra, Rakesh K. ; Tan, Bruce K. ; Peters, Anju T. ; Grammer, Leslie C. ; Kato, Atsushi ; Harris, Kathleen E. ; Carter, Roderick G. ; Fujieda, Shigeharu ; Kern, Robert C. ; Schleimer, Robert P. / Cytokines in chronic rhinosinusitis role in eosinophilia and aspirin-exacerbated respiratory disease. In: American journal of respiratory and critical care medicine. 2015 ; Vol. 192, No. 6. pp. 682-694.
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abstract = "Rationale: The mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD) are not clear. Objectives: To first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and then to investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within nasal polyp (NP) tissues. Methods: Expression levels of numerous inflammatory mediators were determined by quantitative real-time polymerase chain reaction, ELISA, and multiplex immunoassay. Measurements and Main Results: CRSwNP NP had increased levels of type 2 mediators, including IL-5 (P<0.001), IL-13 (P<0.001), eotaxin-2 (P <0.001), and monocyte chemoattractant protein (MCP)-4 (P<0.01), compared with sinonasal tissue from subjects with CRSsNP and control subjects. Expression of IFN-γ messenger RNA or protein was low and not different among the chronic rhinosinusitis subtypes examined. Compared with CRSwNP, AERD NP had elevated protein levels of eosinophil cationic protein (ECP) (P< 0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (P< 0.01), and MCP-1 (P = 0.01), as well as decreased gene expression of tissue plasminogen activator (tPA) (P = 0.02). Despite the higher eosinophilia in AERD, there was no associated increase in type 2 mediator protein levels observed. Conclusions: CRSwNP was characterized by a predominant type 2 inflammatory environment, whereas CRSsNP did not reflect a classic type 1 milieu, as has been suggested previously. AERD can be distinguished from CRSwNP by elevated ECP levels, but this enhanced eosinophilia is not associated with elevations in traditional type 2 inflammatory mediators associated with eosinophil proliferation and recruitment. However, other factors, including GM-CSF, MCP-1, and tPA, may be important contributors to AERD pathogenesis.",
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author = "Stevens, {Whitney W.} and Ocampo, {Christopher J.} and Sergejs Berdnikovs and Masafumi Sakashita and Mahboobeh Mahdavinia and Lydia Suh and Tetsuji Takabayashi and Norton, {James E.} and Hulse, {Kathryn E.} and Conley, {David B.} and Chandra, {Rakesh K.} and Tan, {Bruce K.} and Peters, {Anju T.} and Grammer, {Leslie C.} and Atsushi Kato and Harris, {Kathleen E.} and Carter, {Roderick G.} and Shigeharu Fujieda and Kern, {Robert C.} and Schleimer, {Robert P.}",
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Cytokines in chronic rhinosinusitis role in eosinophilia and aspirin-exacerbated respiratory disease. / Stevens, Whitney W.; Ocampo, Christopher J.; Berdnikovs, Sergejs; Sakashita, Masafumi; Mahdavinia, Mahboobeh; Suh, Lydia; Takabayashi, Tetsuji; Norton, James E.; Hulse, Kathryn E.; Conley, David B.; Chandra, Rakesh K.; Tan, Bruce K.; Peters, Anju T.; Grammer, Leslie C.; Kato, Atsushi; Harris, Kathleen E.; Carter, Roderick G.; Fujieda, Shigeharu; Kern, Robert C.; Schleimer, Robert P.

In: American journal of respiratory and critical care medicine, Vol. 192, No. 6, 15.09.2015, p. 682-694.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cytokines in chronic rhinosinusitis role in eosinophilia and aspirin-exacerbated respiratory disease

AU - Stevens, Whitney W.

AU - Ocampo, Christopher J.

AU - Berdnikovs, Sergejs

AU - Sakashita, Masafumi

AU - Mahdavinia, Mahboobeh

AU - Suh, Lydia

AU - Takabayashi, Tetsuji

AU - Norton, James E.

AU - Hulse, Kathryn E.

AU - Conley, David B.

AU - Chandra, Rakesh K.

AU - Tan, Bruce K.

AU - Peters, Anju T.

AU - Grammer, Leslie C.

AU - Kato, Atsushi

AU - Harris, Kathleen E.

AU - Carter, Roderick G.

AU - Fujieda, Shigeharu

AU - Kern, Robert C.

AU - Schleimer, Robert P.

PY - 2015/9/15

Y1 - 2015/9/15

N2 - Rationale: The mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD) are not clear. Objectives: To first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and then to investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within nasal polyp (NP) tissues. Methods: Expression levels of numerous inflammatory mediators were determined by quantitative real-time polymerase chain reaction, ELISA, and multiplex immunoassay. Measurements and Main Results: CRSwNP NP had increased levels of type 2 mediators, including IL-5 (P<0.001), IL-13 (P<0.001), eotaxin-2 (P <0.001), and monocyte chemoattractant protein (MCP)-4 (P<0.01), compared with sinonasal tissue from subjects with CRSsNP and control subjects. Expression of IFN-γ messenger RNA or protein was low and not different among the chronic rhinosinusitis subtypes examined. Compared with CRSwNP, AERD NP had elevated protein levels of eosinophil cationic protein (ECP) (P< 0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (P< 0.01), and MCP-1 (P = 0.01), as well as decreased gene expression of tissue plasminogen activator (tPA) (P = 0.02). Despite the higher eosinophilia in AERD, there was no associated increase in type 2 mediator protein levels observed. Conclusions: CRSwNP was characterized by a predominant type 2 inflammatory environment, whereas CRSsNP did not reflect a classic type 1 milieu, as has been suggested previously. AERD can be distinguished from CRSwNP by elevated ECP levels, but this enhanced eosinophilia is not associated with elevations in traditional type 2 inflammatory mediators associated with eosinophil proliferation and recruitment. However, other factors, including GM-CSF, MCP-1, and tPA, may be important contributors to AERD pathogenesis.

AB - Rationale: The mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD) are not clear. Objectives: To first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and then to investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within nasal polyp (NP) tissues. Methods: Expression levels of numerous inflammatory mediators were determined by quantitative real-time polymerase chain reaction, ELISA, and multiplex immunoassay. Measurements and Main Results: CRSwNP NP had increased levels of type 2 mediators, including IL-5 (P<0.001), IL-13 (P<0.001), eotaxin-2 (P <0.001), and monocyte chemoattractant protein (MCP)-4 (P<0.01), compared with sinonasal tissue from subjects with CRSsNP and control subjects. Expression of IFN-γ messenger RNA or protein was low and not different among the chronic rhinosinusitis subtypes examined. Compared with CRSwNP, AERD NP had elevated protein levels of eosinophil cationic protein (ECP) (P< 0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (P< 0.01), and MCP-1 (P = 0.01), as well as decreased gene expression of tissue plasminogen activator (tPA) (P = 0.02). Despite the higher eosinophilia in AERD, there was no associated increase in type 2 mediator protein levels observed. Conclusions: CRSwNP was characterized by a predominant type 2 inflammatory environment, whereas CRSsNP did not reflect a classic type 1 milieu, as has been suggested previously. AERD can be distinguished from CRSwNP by elevated ECP levels, but this enhanced eosinophilia is not associated with elevations in traditional type 2 inflammatory mediators associated with eosinophil proliferation and recruitment. However, other factors, including GM-CSF, MCP-1, and tPA, may be important contributors to AERD pathogenesis.

KW - CRSsNP

KW - CRSwNP

KW - Eosinophil

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DO - 10.1164/rccm.201412-2278OC

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