OBJECTIVETo evaluate the expressions of interleukin (IL) 13 and its receptor IL-13Rα2 in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and non-ECRSwNP and their clinicopathological implications.

METHODSA total of 60 consecutive patients with CRSwNP who underwent endoscopic sinus surgery (ESS) were divided into two groups of ECRSwNP (n = 27) and non-ECRSwNP (n = 33) based on tissue eosinophil count (more than five cells per high power field) with postoperative pathological examination. Before ESS,the severities of symptoms, nasal polyps, and sinonasal diseases on CT were scored, peripheral blood eosinophil count and percentage, and total serum. IgE level were measured. IL-13 and IL-13Rα2 expressions in polyp tissues were examined with immunohistochemistry. SPSS 16.0 software was used to analyze the data.

RESULTSThere was no significant differences between ECRSwNP and non-ECRSwNP groups in the mean symptom scores (t = 0.102, P > 0.05), but ECRSwNP, compared to non- ECRSwNP, demonstrated a higher incidence of bilateral polyps (χ2 = 15.879, P < 0.01), a higher mean score of nasal polyps (3.6 ± 1.1 vs 2.1 ± 0.8, t = 4.009, P < 0.01) or diseases on CT (t = 4.428, P < 0.01). And also a significant difference existed between two groups in mean blood eosinophil count (t = 3.148, P < 0.01) or percentage (t =3.038, P < 0.01), but no significant difference in total serum levels of IgE (t = 0.659, P > 0.05). There was a closed correlation between tissue eosinophil count and blood eosinophil count (r = 0.683, P < 0.01) or percentage (r = 0.631, P < 0.01) in ECRSwNP, but not in non-ECRSwNP. The expressions of both IL-13 and IL-13Rα2 increased significantly in ECRSwNP compared to non-ECRSwNP ( scores 8.1 ± 1.6 vs. 5.4 ± 1.6; 8.8 ± 1.4 vs. 4.8 ± 1.6, t value was 4.749, 8.010, P < 0.01).

CONCLUSIONSIL-13 and IL-13Rα2 are associated closely with pathogenesis o ECRSwNP. Subtyping CRSwNP and studying underly mechanism can be helpful to make treatment strategy for CRSwNP.

Chronic Disease ; Eosinophils ; Humans ; Interleukin-13 ; metabolism ; Interleukin-13 Receptor alpha2 Subunit ; metabolism ; Leukocyte Count ; Nasal Polyps ; metabolism ; Paranasal Sinuses ; Rhinitis ; metabolism ; Sinusitis ; metabolism

Idiopathic interstitial pneumonia (IIP) is characterized by varying degrees of interstitial fibrosis. IL-13 and IL-4 are strong inducers of tissue fibrosis, whereas IFN-gamma has antifibrotic potential. However, the roles of these substances in IIP remain unknown. IL-13, IL-4, and IFN-gamma were measured in the BAL fluid of 16 idiopathic pulmonary fibrosis (IPF) patients, 10 nonspecific interstitial pneumonia (NSIP) patients, and 8 normal controls. The expression of IL-13 and IL-13Ralpha1/alpha2 in lung tissues was analyzed using ELISA and immunohistochemistry. IL-13 levels were significantly higher in IPF patients than the others (P<0.05). IL-4 levels were higher in both IPF and NSIP patients than in normal controls (P<0.05), and IFN-gamma levels were lower in NSIP patients than in normal controls (P=0.047). IL-13 levels correlated inversely with FVC% (r=-0.47, P=0.043) and DLCO% (r=-0.58, P=0.014) in IPF and NSIP patients. IL-13 was strongly expressed in the smooth muscle, bronchial epithelium, alveolar macrophages and endothelium of IPF patients. IL-13Ralpha1, rather than IL-13Ralpha2, was strongly expressed in the smooth muscle, bronchial epithelium, and endothelium of IPF patients. IL-13 and its receptors may contribute to the pathogenesis of fibrosis in IIP and appear to be related to the severity of the disease.
Adult ; Female ; Humans ; Idiopathic Interstitial Pneumonias/diagnosis/*metabolism ; Idiopathic Pulmonary Fibrosis/diagnosis/*metabolism ; Interferon-gamma/analysis ; Interleukin-13/*analysis ; Interleukin-13 Receptor alpha1 Subunit/*metabolism ; Interleukin-13 Receptor alpha2 Subunit/*metabolism ; Interleukin-4/analysis ; Lung/physiopathology ; Male ; Middle Aged

BACKGROUNDType 2 cytokine interleukin (IL)-13 and its decoy receptor, IL-13 receptor (R) alpha2 appear to play a major role in tissue fibrosis of schistosomiasis and asthma. IL-13 is a key regulator of the extracellular matrix (ECM). It is known to signal to cells by binding to the IL-13Ralpha1, which then heterodimerizes with IL-4Ralpha. In contrast, IL-13Ralpha2 binds IL-13 with high affinity but does not signal. IL-13Ralpha2 is known to down-regulate granulomatous inflammation and prolong host survival in Schistosoma mansoni (S. mansoni) infection, but little is known about the location and expression level of IL-13Ralpha2 in the context of S. japonicum infection.

METHODSWe established S. japonicum-infected mouse models. Kinetic serum levels of IL-13Ralpha2 were examined with ELISA. IL-13Ralpha2 mRNA and protein of liver tissues were determined by PCR and immunoblotting analysis, respectively. Detection of IL-13Ralpha2 expression and location in macrophages was performed by TaqMan PCR and fluorescent immunocytochemistry technique, respectively.

RESULTSA marked elevation of mRNA and protein expression of IL-13Ralpha2 was observed in mice during S. japonicum infection. An enhanced expression of IL-13Ralpha2 was further demonstrated in primary macrophages of murine schistosomiasis.

CONCLUSIONSIL-13Ralpha2 in macrophages may be a critical contributor to pathogenesis of schistosomiasis. The data highlight the potential importance of cell signaling and antifibrotic gene therapeutics in T helper 2 cell (Th2)-mediated diseases.

Animals ; Blotting, Western ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Female ; Interleukin-13 Receptor alpha2 Subunit ; metabolism ; Macrophages ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction ; Schistosoma japonicum ; pathogenicity ; Schistosomiasis japonica ; immunology ; microbiology