标题：Cytokines in Chronic Rhinosinusitis: Role in Eosinophilia and Aspirin Exacerbated Respiratory Disease

作者：Stevens WWOcampo CJBerdnikovs SSakashita MMahdavinia MSuh LTakabayashi TNorton JEHulse KEConley DBChandra RKTan BKPeters ATGrammer Iii LCKato AHarris KECarter RGFujieda SKern RCSchleimer RP

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• 文献摘要：

RATIONALE:

The mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), with nasal polyps (CRSwNP) and aspirin exacerbated respiratory disease (AERD) are not clear.

OBJECTIVE:

To first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and to then investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within NP tissues.

METHODS:

Expression levels of numerous inflammatory mediators were determined by qRT-PCR, 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 MCP-4 (p<0.01) compared to sinonasal tissue from CRSsNP and controls. Expression of IFNγ mRNA or protein was low and not different among CRS subtypes examined. Compared to CRSwNP, AERD NP had elevated protein levels of ECP (p<0.001), GM-CSF (p<0.01), and MCP-1 (p=0.01) as well as decreased gene expression of tissue plasminogen activator (t-PA) (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 while CRSsNP did not reflect a classic type-1 milieu, as has been previously suggested. 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 t-PA may be important contributors to AERD pathogenesis.

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