Efficacy of Whole-Blood Exchange Transfusion in Refractory Severe Autoimmune Haemolytic Anaemia Secondary to Systemic Lupus Erythematosus: A Real-World Observational Retrospective Study.

Background: Severe autoimmune haemolytic anaemia (AIHA) in systemic lupus erythematosus (SLE) patients could be life-threatening and formidable, especially in those nonresponsive to glucocorticoids (GCs) and immunosuppressants (ISAs). Whole-blood exchange transfusion (WBE), with plasma exchange and pathogenic cell removal as well as healthy red blood cell transfusion, could be beneficial. The objective of this study was to investigate the efficacy and safety of WBE in combination with GCs/ISAs. Methods: In this retrospective study, the clinical data of 22 refractory severe SLE-AIHA inpatients between February 2016 and February 2021 were collected and analysed, among whom 14 patients had received WBE and were compared with those treated with typical second-line therapy of intravenous immunoglobulin and/or rituximab (IVIG/RTX). Results: Among the 22 severe refractory SLE-AIHA patients, eight patients received IVIG and/or RTX without WBE (group 1, IVIG/RTX, n = 8), seven patients were given WBE without IVIG/RTX (group 2, WBE alone, n = 7), and seven patients who failed initial IVIG/RTX therapy were given sequential WBE therapy (group 3 IVIG/RTX→WBE, n = 7). Fourteen patients had accepted WBE treatment regardless of prior IVIG/RTX usage (group 2 + 3, WBE ± IVIG/RTX, n = 14). On days 1, 3, 5, and 7 after corresponding therapies, patients of groups 2, 3, and 2 + 3 showed significantly higher levels of haemoglobin (Hb) than patients of group 1. Compared with patients of group 1, patients of groups 2, 3, and 2 + 3 took less time to reach and maintain Hb ≥60 g/L from baseline. Groups 2 and 2 + 3 consumed a lower dose of GCs than group 1 to reach and maintain Hb ≥60 g/L from baseline. Group 1 experienced longer hospital stays than group 2, and group 3's cost of hospitalisation is more than groups 1 and 2. Hbmin <40 g/L may be a key indicative factor for initiating WBE remedy therapy as IVIG/RTX may not be effective enough in 48-72 h in those patients with refractory severe SLE-AIHA. No severe adverse effects were observed in the WBE group. Conclusions: WBE could be a safe and beneficial alternative therapy for refractory severe SLE-AIHA.

A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis.

BACKGROUND: Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA. METHODS: Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48. RESULTS: At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed. CONCLUSIONS: This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted. TRIAL REGISTRATION: Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.

Rapid Onset of Efficacy of Baricitinib in Chinese Patients with Moderate to Severe Rheumatoid Arthritis: Results from Study RA-BALANCE.

INTRODUCTION: Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate. METHODS: This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4 mg once daily compared with placebo, based on data from a phase 3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks 1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4 weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively. RESULTS: Statistically significant (p ≤ 0.05) improvements were observed as early as week 1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week 4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24 weeks. CONCLUSIONS: Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02265705.

An Autoimmunogenic and Proinflammatory Profile Defined by the Gut Microbiota of Patients With Untreated Systemic Lupus Erythematosus.

OBJECTIVE: Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in-depth understanding of the contribution of gut microbiota to the immunopathogenesis of SLE. METHODS: Fecal metagenomes from 117 patients with untreated SLE and 52 SLE patients posttreatment were aligned with 115 matched healthy controls and analyzed by whole-genome profiling. For comparison, we assessed the fecal metagenome of MRL/lpr mice. The oral microbiota origin of the gut species that existed in SLE patients was documented by single-nucleotide polymorphism-based strain-level analyses. Functional validation assays were performed to demonstrate the molecular mimicry of newly found microbial peptides. RESULTS: Gut microbiota from individuals with SLE displayed significant differences in microbial composition and function compared to healthy controls. Certain species, including the Clostridium species ATCC BAA-442 as well as Atopobium rimae, Shuttleworthia satelles, Actinomyces massiliensis, Bacteroides fragilis, and Clostridium leptum, were enriched in SLE gut microbiota and reduced after treatment. Enhanced lipopolysaccharide biosynthesis aligned with reduced branched chain amino acid biosynthesis was observed in the gut of SLE patients. The findings in mice were consistent with our findings in human subjects. Interestingly, some species with an oral microbiota origin were enriched in the gut of SLE patients. Functional validation assays demonstrated the proinflammatory capacities of some microbial peptides derived from SLE-enriched species. CONCLUSION: This study provides detailed information on the microbiota of untreated patients with SLE, including their functional signatures, similarities with murine counterparts, oral origin, and the definition of autoantigen-mimicking peptides. Our data demonstrate that microbiome-altering approaches may offer valuable adjuvant therapies in SLE.

Integration of microRNA and mRNA expression profiles in the skin of systemic sclerosis patients.

MicroRNAs (miRNAs) play important roles in the fibrosis of systemic sclerosis (SSc). However, the underlying miRNA-mRNA regulatory network is not fully understood. A systemic investigation of the role of miRNAs would be very valuable for increasing our knowledge of the pathogenesis of SSc. Here, we combined miRNA and mRNA expression profiles and bioinformatics analyses and then performed validation experiments. we identified 21 miRNAs and 2698 mRNAs that were differentially expressed in SSc. Among these, 17 miRNAs and their 33 target mRNAs (55 miRNA-mRNA pairs) were involved in Toll-like receptor, transforming growth factor ß and Wnt signalling pathways. Validation experiments revealed that miR-146b, miR-130b, miR-21, miR-31 and miR-34a levels were higher whereas miR-145 levels were lower in SSc skin tissues and fibroblasts, normal fibroblasts and endothelial cells that were stimulated with SSc serum. ACVR2B, FZD2, FZD5 and SOX2 levels were increased in SSc skin fibroblasts, normal fibroblasts and endothelial cells that were stimulated with SSc serum. We did not identify any negative correlations among these miRNA-mRNA pairs. miR-21 was specifically expressed at higher levels in SSc serum. Six miRNAs and 4 mRNAs appear to play important roles in the pathogenesis of SSc are worth investigating in future functional studies.

Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis.

OBJECTIVE: Total glucosides of paeony (TGP) have been confirmed to exert anti-inflammatory and hepatoprotective effects. Methotrexate (MTX) and Leflunomide (LEF) combination has a better efficacy in the treatment of active rheumatoid arthritis (RA), but hepatotoxicity was observed. In this study, we investigated the effect of TGP on hepatic dysfunction caused by MTX and LEF in patients with active RA. METHODS: A total of 268 patients with active RA (disease activity score in 28 joints, DAS28>3.2) were enrolled in this study. All patients were randomly assigned to two groups, the therapeutic group in which patients were treated with TGP (1.8 g/day) combined with MTX and LEF (MTX 10mg/week plus LEF 20mg/day) while in the control group, patients were treated without TGP up to 12 weeks. The efficacy and liver abnormalities were observed. RESULTS: The incidence of abnormal liver function within 12 weeks in TGP group was significantly lower than that in control group (11.38% vs 23.26%, P=0.013). The proportion of patients with ALT/AST >3 times ULN (upper limits of normal) was significantly lower in TGP group than control group (1.63% vs 7.75%, P=0.022). More patients achieved remission, good and moderate response in TGP group than control group at 4, 8 and 12 weeks, but the difference was not significant (P>0.05). The proportions of all adverse events were comparable in the two groups except for diarrhea. CONCLUSIONS: Our study demonstrates that TGP can significantly reduce the incidence and severity of liver damage caused by MTX+LEF in the treatment of active RA patients.

Ischemic postconditioning protects cardiomyocytes against ischemia/reperfusion injury by inducing MIP2.

Cardiomyocytes can resist ischemia/reperfusion (I/R) injury through ischemic postconditioning (IPoC) which is repetitive ischemia induced during the onset of reperfusion. Myocardial ischemic preconditioning up-regulated protein 2 (MIP2) is a member of the WD-40 family proteins, we previously showed that MIP2 was up-regulated during ischemic preconditioning (IPC). As IPC and IPoC engaged similar molecular mechanisms in cardioprotection, this study aimed to elucidate whether MIP2 was up-regulated during IPoC and contributed to IPoC-mediated protection against I/R injury. The experiment was conducted on two models, an in vivo open chest rat coronary artery occlusion model and an in vitro model with H9c2 myogenic cells. In both models, 3 groups were constituted and randomly designated as the sham, I/R and IPoC/hypoxia postconditioning (HPoC) groups. In the IPoC group, after 45 min of ischemia, hearts were allowed three cycles of reperfusion/ischemia phases (each of 30 s duration) followed by reperfusion. In the HPoC group, after 6 h of hypoxia, H9c2 cells were subjected to three cycles of 10 minute reoxygenation and 10 minute hypoxia followed by reoxygenation. IPoC significantly reduced the infarct size, plasma level of Lactate dehydrogenase and creatine kinase MB in rats. 12 h after the reperfusion, MIP2 mRNA levels in the IPoC group were 10 folds that of the sham group and 1.4 folds that of the I/R group. Increased expression of MIP2 mRNA and attenuation of apoptosis were similarly observed in the HPoC group in the in vitro model. These effects were blunted by transfection with MIP2 siRNA in the H9c2 cells. This study demonstrated that IPoC induced protection was associated with increased expression of MIP2. Both MIP2 overexpression and MIP2 suppression can influence the IPoC induced protection.

Elevation of human tumor necrosis factor-like weak inducer of apoptosis in peripheral blood mononuclear cells is correlated with disease activity and lupus nephritis in patients with systemic lupus erythematosus.

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a recently identified proinflammatory cytokine of the TNF superfamily. Studies have indicated that TWEAK plays an important role in renal, vascular injury and immune disease. The aim of this study was to explore the expression of the TWEAK in peripheral blood mononuclear cells (PBMCs) and analyze the correlation between TWEAK and disease activity and renal damage of SLE. The expression of TWEAK in PBMCs was determined by RT-PCR and western blot. SLE disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 score. Next were analyzed the correlations of TWEAK mRNA and protein to serum IL-10, MCP-1 and some laboratory parameters of SLE disease activity. Subjects comprised 48 patients with SLE including 25 patients with renal damage and 23 without, 20 patients with rheumatoid arthrithis (RA) and 15 healthy controls. The results showed that TWEAK expressions in PBMCs from SLE patients were significantly higher than that in RA patients or healthy controls, especially higher in those patients with renal disease. Elevated production of TWEAK is correlated positively and significantly with SLEDAI, proteinuria, serum anti-dsDNA, IL-10 and MCP-1, but inversely associated with serum complements. Our results suggested that TWEAK in PBMCs is positively related to SLE disease activity and might be involved in the pathogenesis of SLE.

Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus.

We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 x 10(-25) < or = P(combined) < or = 2.77 x 10(-8)) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 x 10(-42) < or = P(combined) < or = 5.18 x 10(-12)). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.

[The plasmic translocation and release of high mobility group box chromosomal protein 1 in peripheral blood monocytes of patients with rheumatoid arthritis and the effect of thalidomide].

OBJECTIVE: To investigate the release and intracellular localization of high mobility group box chromosomal protein 1 (HMGB1) in the peripheral blood monocytes of rheumatoid arthritis (RA) patients and the inhibitive effect of thalidomide. METHODS: 19 RA patients and 20 healthy controls were included in the study. Monocytes were separated from peripheral blood with Ficoll density gradient centrifugation. Monocytes were treated with 100 ng/ml tumor necrosis factor alpha (TNFalpha) or 100 ng/ml TNFalpha plus 40 microg/ml thalidomide and grown in an incubator at 37 degrees C with 5% CO2 for 24 hours. The culture supernatants of the monocytes were collected. HMGB1 level in the culture medium was detected with Western blot. In addition, the intracellular localization of HMGB1 in the monocytes was investigated with immunocytochemical analysis. RESULTS: Without stimulation, the release of HMGB1 protein was significantly increased in the culture supernatants of peripheral blood monocytes from RA patients as compared with that from healthy controls (P < 0.05). TNFalpha (100 ng/ml) did not further increase the release of HMGB1 in the monocytes from the patients with RA. Thalidomide (40 microg/ml) could inhibit the release of HMGB1 in the monocytes from RA patients stimulated with TNFalpha (P < 0.05). In the monocytes from RA patients, HMGB1 was mainly localized in the nucleus. Treatment with TNFalpha (100 ng/ml) for 24 hours resulted in a cytoplasmic translocation of HMGB1, which was inhibited significantly by thalidomide. CONCLUSION: TNFalpha induces the release and cytoplasmic translocation of HMGB1 in the peripheral blood monocytes of RA patients and thalidomide inhibits the release and translocation of HMGB1.

[Expression of high mobility group box chromosomal protein 1 in peripheral blood of patients with rheumatoid arthritis].

OBJECTIVE: To investigate the mRNA and protein expression of high mobility group box chromosomal protein 1 (HMGB1) in peripheral blood mononuclear cells (PBMCs) and serum. METHODS: Levels of HMGB1mRNA were detected with reverse transcription polymerase chain reaction (RT-PCR) in PBMC and levels of HMGB1 protein in PBMC and plasm were measured with Western blot in 38 patients with active rheumatoid arthritis (RA), 24 with inactive RA and 20 healthy controls. Ficoll density gradient centrifugation was used to separate PBMCs from peripheral blood. The correlation between the levels of HMGB1 in serum and the index of disease activity in RA was analyzed. RESULTS: There was no statistically significant difference of the mRNA expression of HMGB1 in PBMCs from active RA patients as compared with those from inactive RA group and healthy controls (F = 1.23, P > 0.05). The protein expression of HMGB1 was significantly lower in PBMCs from active RA patients (F = 70.91, P < 0.01), while the protein expression of HMGB1 was higher in plasma from active RA patients (P < 0.001) as compared with that from inactive RA patients and healthy controls. However, there was no statistically significant difference between inactive RA patients and healthy controls (P > 0.05). The level of HMGB1 protein in plasma of RA patients was correlated with erythrocyte sedimentation rate (ESR) (r(s) = 0.478, P < 0.001) and C- reactive protein (CRP) (r(s) = 0.574, P < 0.05). It was not correlated with age, the number of tender joints and swollen joints, radiographic scores and therapeutic effect. CONCLUSION: The protein expression of HMGB1 was significantly decreased in PBMCs from active RA patients, while it was increased in serum from active RA patients. HMGB1 plays a pivotal role in the pathogenesis of RA and may be a target of therapy as a novel cytokine.

[Echocardiographic changes and anticardiolipin antibodies in patients with systemic lupus erythematosus].

OBJECTIVE: To analyze the echocardiographic abnormalities and the prevalence of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE) patients and to evaluate the relationship between aCL and cardiac valvular abnormalities in SLE patients. METHODS: Ninety SLE patients were performed M-mode, 2-dimensional and Doppler echocardiography and aCL IgG and IgM were measured by an enzyme-linked immunosorbent assay (ELISA). According to the abnormalities in the echocardiography, the patients were assigned into valvular abnormality group and non-valvular abnormality group. Chi-square method was used to compare the difference of aCL prevalence between the two groups. RESULTS: The prevalence of echocardiographic abnormalities was 53.33%, and valvular abnormality (38.89%) and pericardial effusion (34.44%) presented most frequently. The aCL prevalence was 32.56% in the 43 SLE patients. The prevalence of aCL in the valvular abnormality group was significantly higher than that in non-valvular abnormality group (52.94% vs 19.23%, P<0.05). CONCLUSION: The incidence of echocardiographic abnormalities is high in SLE patients, most often in valves and pericardium. The aCL is probably related to valvular damage in SLE patients.

[Effect of bizhongxiao decoction on the expression of 2-dimensional polyacrylamide gel electrophoresis protein in the synovial tissue with collagen-induced arthritis in rats].

OBJECTIVE: To explore the effect of bizhongxiao decoction (BZXD) on the protein maps of BZXD-treated synovitis of collagen-induced arthritis (CIA) in rats in 2-dimensional gel electrophoresis (2-DE), and to provide new clues for illuminating the active mechanism of BZXD in treating the rheumatoid arthritis (RA). METHODS: Seventy SD rats were randomly divided into nor- mal group, model group and BZXD group. The experimental arthritis rat model was established by subcutaneouly injecting Type II collagen and complete Freunds adjuvant. The total proteins of synovial tissue of rat joints in the normal group, model group and BZXD group were seperated by 2-DE respectively. The gels of the 3 groups were stained by Coomassie brilliant blue. Electron pictures were obtained by scanning the gels, and then the differential proteins among the normal group, model group and BZXD group were examined by comparing the spots density volume in the gels. The electrophoregrams of the gels were analyzed in Pdquest software. RESULTS: The incidence of arthritis in the rats was approximately 88%. The 2-DE maps of rat synovial tissue in the normal group, model group and BZXD group were well duplicated. The average protein spots in the normal group, model group and BZXD group were 947 +/- 39, 994 +/- 41, and 1031 +/- 52, and the match rates were 92%, 91%, and 94.2% respectively. The average deviations of spot position were (0.896 +/- 0.217) mm in isoelectric focusing (IEF) and (1.102 +/- 0.104) mm in sodiumdo-decylsufate-polyacrylamide gel electrophoresis (SDS-PAGE), respectively. Three hundred twenty-eight differential proteins were observed between the model group and BZXD group, of which 174 were up-regulated, 147 were down-regulated in the BZXD group, and 7 proteins were expressed only in the model group. One hundred ninty-three differential proteins were displayed between the model group and the normal group, of which 123 proteins were up-regulated and 70 were down-regulated in the model group. CONCLUSION: 2-DE protein expression profiles of synovial tissue in CIA rats are established, and many differential proteins are discovered. Further analysis on the differential proteins may serve as a new method to study the moleculer mechanism of BZXD in treating the rheumatoid arthritis.

[Clinical analysis of pregnancy complicated with systemic lupus erythematosus].

OBJECTIVE: To investigate the interacting effects between pregnancy and flares of systemic lupus erythematosus (SLE) and to explore the best occasion for SLE patients' conception and the management during the pregnancy. METHODS: Thirty one cases of pregnancy complicated with SLE were investigated retrospectively, among whom 18 were in remission of SLE at the beginning of conception (Group A), and the other 13 either had high-activity of the disease or were first diagnosed as SLE during the pregnancy (Group B). Various doses of prednisone were administered to control SLE. RESULTS: SLE flares still occurred in 6 cases in Group A, but in all cases in Group B. Compared with Group A, the rates of fetal loss and early delivery were significantly higher in Group B (P < 0.05), while the survival rate and the weight of the new born were notably decreased in Group B (P < 0.05). CONCLUSION: Pregnancy and SLE interacted with each other unfavorably. Selection of remission stage for conception and proper management during the pregnancy could significantly improve the maternal-fetal safety.

[Effect of bee venom on adjuvant induced arthritis in rats].

OBJECTIVE: To investigate the anti-arthritic effect of bee venom in adjuvant induced arthritis (AIA) in rats. METHODS: Thirty-two male SD rats were enrolled in the experiment. Six were treated as negative controls and 20 AIA models were randomly divided into 3 groups: model controls (n=6), sodium chloride treatment group (n=6), and bee venom treatment group (n=8). The rats in the model control were killed before the treatment and the peripheral blood and synovium samples were collected for pre-treatment controls. The rats in the bee venom treatment group were injected hypodermically with bee venom for 14 days, while those in the sodium chloride treatment group were treated with the same volume of sodium chloride. During this period, the circumference of the affected joints and the total scores of the joints in all groups were measured every 2 days and X ray examinations were performed before and after the treatment. At the end of the treatment, all the rats were killed and their peripheral blood and synovium samples were collected for measurements of tumor necrosis factor TNF-alpha and interleukin IL-1 beta and histological studies, respectively. RESULTS: Compared with the sodium chloride group, the rats in the bee venom treatment group were less swollen in joints and circumference of joints and lower joint scores decreased (P<0.05). At the same time, the bone erosion and the infiltration of inflammatory cells in the synovium were also significantly reduced in the bee venom treatment group. In addition, the serum concentrations of TNF-alpha and IL-1 beta were significantly lower in rats of the bee venom treatment group than those of the sodium chloride group (P<0.05 and P<0.01, respectively). CONCLUSION: Bee venom is effective in treating AIA by reducing synovitis, downregulating the serum concentrations of cytokine TNF-alpha and IL-1 beta and alleviating the bone erosion.