| Objective: Rheumatoid arthritis (RA) is a kind of autoimmune diseasecharacterized by erosive synovitis. RA eventually lead to the destruction ofbone and cartilage. Its main clinical feature is the symmetry of the multi jointswelling, tenderness, and functional decline. The etiology and pathogenesis ofRA is uncompletely known. Recent evidence suggests that the infectionfactors, genetic factors, T lymphocytes, B lymphocytes and synovial cells areinvolved in the pathogenesis of RA. In the present study showed that manycytokines are involved in the pathogenesis of RA. It has been foucs on thatIL-33may play an important role in the pathogenesis of RA. Recently, IL-33was recognized as a novel IL-1family member. However, in contrast to IL-1and IL-18, which predominantly promote Th1-type responses, IL-33mainlyinduces Th2cytokines. IL-33can promote Th2cells to secrete Th2-typecytokines such as IL-4, IL-13. IFN-γ is a typical cytokine of Th1-type. Theaim of this study is to further explore the correlation between IL-33and RA,through investigate the expression of IL-33, IL-4, IL-13and IFN-γ in serum ofRA and analysis the correlation between the serum cytokines levels andclinical activity index.Methods:30RA patients and21control person were enrolled the study.30RA patients who diagnosed for the first time in our department from March2010to October2011. The classification of all RA patients were consistentwith American Rheumatism Institute and European congress preventionfederation rheumatoid arthritis diagnostic criteria of2009. All patients wereinitial diagnosis and treatment. RA patients were never received immunosupprssive treatment, such as Glucocorticoid (GC), disease modifyingantirheumatic drugs (DMARDs), biologic agent and other intervention therapy.21healthy adult as control were chosen. There was no obvious statistical difference in gender and age distribution between the two groups (P>0.05).Serum was taken from all the patients and normal controls. Clinic indexes ofpatients with rheumatoid arthritis were recorded such as age, gender, diseaseduration, clinical symptoms, RF, ESR, CRP, PLT, etc. Calculated DAS28score. Avidin biotin peroxidase complex enzyme-linked immunosorbent assay(ABC-ELISA) was used to measure the levels of IL-33, IL-4, IL-13and IFN-γin serum, and compared with that of normal control. To further analysis thecorrelation between these cytokines and clinical indicators.Data were analyzed by statistical software SPSS17.0for windows. Themean number±standard deviation (x±ｓ) or M(QR) was used to express themeasurement data. The t or t' test was adopted for mean comparison. Linearcorrelation analysis was performed for correlationship. P value<0.05wasconsidered significant.Results:1General data description: The case group contained18female patients and12male patients. The average age was (55.37±10.46) years. There were7patients (3male patients,4female patients) complicated with pulmonaryinterstitial fibrosis. The control group contained11female and10male. Theaverage age was (49.76±9.959) years. There were no significant differencesbetween the patients and normal controls in age and gender distribution(P>0.05). RA group, the mean of ESR, CRP, RF, PLT and DAS28were(66.80±27.224)mm/h,(50.902±40.157)mg/L,266(316)IU/ml,(338.997±109.231)×109/L,(6.372±1.281).2The serum levels of IL-33, IL-4, IL-13, IFN-γ in RA.2.1The serum levels of IL-33, IL-4, IL-13, IFN-γ in RA patients were(4.673±0.600) ng/L,(66.726±15.582) ng/L,(7.384±1.365) ng/L,(237.247±52.272) ng/L which were significantly higher than normal controls(3.421±1.402) ng/L,(49.429±16.362) ng/L,(5.525±1.765) ng/L,(199.276±64.455) ng/L.(P=0.001; P=0.000; P=0.01; P=0.025).3The comparisons of RA-ILD group with other groups.3.1The comparison of RA combined with pulmonary interstitial fibrosis patients and the other RA patients. The levels of IL-33,IL-4,IL-13,IFN-γ inserum of RA-ILD group were (4.69±0.485) ng/L,(68.847±20.701) ng/L,(7.823±1.266) ng/L,(229.114±60.748) pg/L. The levels of IL-33,IL-4,IL-13,IFN-γ in serum of RA group without ILD were (4.667±0.640) ng/L,(66.081±14.188) ng/L,(7.251±1.393) ng/L,(239.722±50.675) pg/L. Therewere not statistically significant difference between these two groups(P=0.932; P=0.688; P=0.340; P=0.646).3.2The comparison of RA combined with pulmonary interstitial fibrosisgroup and the normal control group: The levels of IL-33, IL-4, IL-13in serumof RA patients were (4.69±0.485) ng/L,(68.847±20.701) ng/L,(7.823±1.266)ng/L, which were significantly higher than healthy control group (3.421±1.402)ng/L,(49.429±16.362) ng/L,(5.525±1.765) ng/L.(P=0.028; P=0.017;P=0.004). The level of IFN-γ in serum of RA patients was(229.114±60.748)ng/L, in serum of normal control group was(199.276±64.455)ng/L. No significant differences between the two groups.(P=0.292).4The correlation between serum levels of IL-33, IL-4,IL-13,IFN-γ and clincalindex.4.1The correlation between serum levels of cytokines, such as IL-33, IL-4,IL-13and IFN-γ. The serum levels of IL-33were positively correlated withthe levels of IL-13and IFN-γ.(r=0.436, P=0.016; r=0.503, P=0.005). Therewas no obvious correlation between serum levels of IL-33, IL-4.(r=0.191,P=0.313); The serum levels of IL-13were positively correlated with the levelsof IL-4, IFN-γ.(r=0.645, P=0.000; r=0.755, P=0.000); The serum levels ofIL-4were positively correlated with the levels of IFN-γ.(r=0.591, P=0.001)4.2The correlation between serum levels of IL-33, IL-4, IL-13, IFN-γ andclinical index of disease (DAS28, RF, ESR, CRP, PLT): According tocorrelation analysis, the levels of IL-33in serum were positively correlatedwith ESR and CRP (r=0.367, P=0.046; r=0.417, P=0.022); The levels ofIL-13in serum were positively correlated with CRP (r=0.461, P=0.010); Thelevels of IFN-γ in serum were positively correlated with CRP (r=0.402, P=0.028); There was no obviously correlation between IL-4and clinical index;There was no obviously correlation between these cytokines and DAS28, RF,PLT.Conclusions:1The levels of IL-33, IL-4, IL-13and IFN-γ in serum significantly increasedin patients with RA. The serum levels of IL-33were positively correlated withthe levels of IL-13and IFN-γ. There was no obvious correlation betweenserum levels of IL-33, IL-4. All above suggesting that the incresed expressionof IL-33may has a certain role in the pathogenesis of RA. IL-33is not onlyinvolved in the regulation of Th2response but also involved in the regulationof Th1response.2The levels of IL-33, IL-4, IL-13in serum significantly increased in RApatients combined pulmonary interstitial fibrosis. The level of IFN-γ in serumhad no dignificantly difference between RA patients combined pulmonaryinterstitial fibrosis and healthy control group. There was no significantlydifferent between these cytokines levels in the comparison of RA combinedwith pulmonary interstitial fibrosis patients and the other RA patients.which suggested that the Th1/Th2imbalance exist and Th2cells prevail in RAcombined pulmonary interstitial fibrosis. IL-33may has a certain role in thepathogenesis of pulmonary interstitial fibrosis.3. The levels of IL-33in serum was positively correlated with ESR and CRP.The levels of IL-13and IFN-γ in serum were positively correlated with CRP.Which suggested that IL-33may be involved in the RA acute phase response.With the participation of the incresed expression of IL-33may aggravate thejoint inflammation. |
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