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ID PMID Title PublicationDate abstract
29868592 Clinical, Imaging, and Pathological Suppression of Synovitis in Rheumatoid Arthritis: Is t 2018 The management of patients with rheumatoid arthritis (RA) has witnessed a dramatic revolution in recent years, and disease remission has become an increasingly achievable outcome. Rheumatologists are now facing the urgent question of whether, once remission has been achieved and stably maintained, drugs can be tapered, and even discontinued. The concept of disease remission however encompasses progressive layers of complexity, all of which need to be disentangled before considering RA as a "curable" condition. As the synovial membrane represents the ultimate target of the pathological process of RA, a critical issue remains whether disease remission coincides with true suppression of inflammation and definitive tissue "healing." In this short review, we will provide a critical summary of recent studies investigating the possibility of controlling RA synovitis at the clinical, imaging or pathological level. Potential advantages and limitations of these perspectives in the definition of remission are also discussed.
29492111 Efficacy and safety of sarilumab in patients with active rheumatoid arthritis. 2018 Mar The mainstay of rheumatoid arthritis (RA) treatment involves the use of medications that slow disease progression and reduce inflammation. Inadequate treatment responses and intolerances to conventional RA treatment have led to the development of biologic agents for the management of moderate-to-severe disease activity. Interleukin-6 (IL-6) inhibition is one of the targets for biologic activity in RA treatment. IL-6 is found in excess in the synovial fluid and contributes to joint erosion through its action on osteoclast cells. Sarilumab is a new IL-6 inhibitor indicated for the treatment of moderate-to-severe RA as monotherapy or in combination with conventional therapies in patients with an inadequate response to previous RA treatment.
28685302 Anti-arthritic activity of cell wall content of Lactobacillus plantarum in freund's adjuva 2018 Feb Alteration of microbiota is related with rheumatoid arthritis (RA) and administration of certain probiotics showed an improvement in RA. The present study was designed to find out the anti-arthritic activity of cell wall content of Lactobacillus plantarum in complete Freund's adjuvant (CFA)-induced arthritis in rats. Freund's adjuvant was injected into the left footpad in female rats on day 0 and dexamethasone (1 mg kg(-1), s.c.) & cell wall content of L. plantarum (10(5), 10(7), and 10(9) cfu/animal, s.c.) treatment were given from day 7 to 21. The change in body weight, paw volume and arthritic index, joint stiffness, gait test, mobility test, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, serum rheumatoid factor (RF), and serum TNF-α was measured on day 21. Cell wall content of L. plantarum treated animals showed improvement in all the parameters as compared to that in CFA-treated animals and exert anti-arthritic activity.
30112130 Severe Sub-Acromial Bursitis with Rice Bodies in a Patient with Rheumatoid Arthritis: A Ca 2018 Jul Multiple rice body formation is a rare presentation of chronic sub-acromial bursitis secondary to extensive underlying rheumatoid arthritis, sero-negative inflammatory arthritis or tuberculous joints. Although there is usually an accompanying inflammatory arthropathy, it can occur in the absence of any underlying systemic disorder. We report a case of five years old neglected rice body deposition in shoulder in a 54-years old lady diagnosed to be having rheumatoid arthritis. After initial investigations, arthroscopic removal of rice bodies with bursa excision relieved the symptoms. The underlying rheumatic condition continued its course, generally sparing the involved shoulder joint. We suggest thorough examination for systemic rheumatologic disease in patients diagnosed with such lesions.
30167326 Distinguishing rheumatoid arthritis from psoriatic arthritis. 2018 Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) have key differences in clinical presentation, radiographic findings, comorbidities and pathogenesis to distinguish between these common forms of chronic inflammatory arthritis. Joint involvement is typically, but not always, asymmetric in PsA, while it is predominantly symmetric in RA. Bone erosions, without new bone growth, and cervical spine involvement are distinctive of RA, while axial spine involvement, psoriasis and nail dystrophy are distinctive of PsA. Patients with PsA typically have seronegative test findings for rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies, while approximately 80% of patients with RA have positive findings for RF and CCP antibodies. Although there is overlap in the pathogenesis of PsA and RA, differences are also present that affect the efficacy of treatment. In PsA, levels of interleukin (IL)-1β, IL-6, IL-17, IL-22, IL-23, interferon-γ and tumour necrosis factor-α (TNF-α) are elevated, and in RA, levels of IL-1, IL-6, IL-22, IL-33, TNF-α, chemokine ligand 11 and chemokine C-X-C motif ligand 13 are elevated. Differences in the pathogenesis of RA and PsA translate into some variances in the specificity and efficacy of therapies.
29495570 Targeting IgG in Arthritis: Disease Pathways and Therapeutic Avenues. 2018 Feb 28 Rheumatoid arthritis (RA) is a polygenic and multifactorial syndrome. Many complex immunological and genetic interactions are involved in the final outcome of the clinical disease. Autoantibodies (rheumatoid factors, anti-citrullinated peptide/protein antibodies) are present in RA patients' sera for a long time before the onset of clinical disease. Prior to arthritis onset, in the autoantibody response, epitope spreading, avidity maturation, and changes towards a pro-inflammatory Fc glycosylation phenotype occurs. Genetic association of epitope specific autoantibody responses and the induction of inflammation dependent and independent changes in the cartilage by pathogenic autoantibodies emphasize the crucial contribution of antibody-initiated inflammation in RA development. Targeting IgG by glyco-engineering, bacterial enzymes to specifically cleave IgG/alter N-linked Fc-glycans at Asn 297 or blocking the downstream effector pathways offers new avenues to develop novel therapeutics for arthritis treatment.
30714481 Clinical and etiological meaning of anti-carbamylated protein antibodies in rheumatoid art 2018 Dec Several autoantibodies against proteins with post-translational modifications have been detected in patients with rheumatoid arthritis (RA) and are called anti-modified protein antibodies (AMPAs). Anti-carbamylated protein antibodies (Anti-CarP Ab) are the second most vigorously researched AMPAs following anti-citrullinated protein/peptide antibodies (ACPA). Anti-CarP Ab and ACPA show cross-reactivity to some extent and frequently co-exist with each other in RA, but are two distinct antibodies. Although the diagnostic efficacy of anti-CarP Ab is inferior to that of ACPA, the diagnostic specificity of RA may improve when used in combination with ACPA and rheumatoid factor. Anti-CarP Ab and ACPA are also useful for identifying patients at high risk of more severe joint destruction and cardiovascular diseases. The high prevalence of the co-existence of both antibodies suggests a common factor in their production, and this is important for the development of RA because both antibodies emerge before the onset of clinical symptoms. Neutrophils may also be crucially involved. It is important to distinguish citrullinated antigens from carbamylated antigens because the methods commonly used to detect the former are now known to be cross-reactive with the latter. Research on anti-CarP Ab will provide novel insights into the pathology and etiology of RA.
30408452 Therapeutic effects of polysaccharides from Anoectochilus roxburghii on type II collagen-i 2019 Feb 1 Anoectochilus roxburghii, a famous Chinese herbal medicine, has been commonly used for the treatment of liver disease, diabetes, and rheumatoid arthritis. Our study aimed to investigate the anti-rheumatoid arthritis effects of A. roxburghii polysaccharides (ARP), using the rat's model of type II collagen-induced arthritis (CIA). ARP was prepared by alcohol sedimentation and structurally characterized based on combined chemical, chromatographic and spectroscopic methods. High Performance Size Exclusion Chromatography-Multiangle Laser Light Scattering-Refrative Index (HPSEC-MALLS-RI) analysis revealed that ARP includes two peaks, and the weight-average molecular weight (Mw) of the principal one was estimated as 5.90 kDa with a relative content of 98.2%. Pharmacological results exhibited that ARP significantly decreased the arthritis index and ameliorated the inflammatory cell infiltration and the synovial tissue destruction in CIA rats. Additionally, ARP possessed significant NO production inhibitory effects and antioxidant activity. Further anti-inflammatory mechanism investigations indicated that ARP significantly inhibited the activation of nuclear factor κB (NF-κB) pathway by suppressing the phosphorylation of IκB and p65, which subsequently down-regulated the mRNA expressions of IL-1β and IL-6 in LPS-stimulated RAW 264.7 cells. These findings suggested that ARP has great potential in the development of functional foods and dietary supplements for the treatment of rheumatoid arthritis.
30564452 Comparing the disease course of patients with seronegative and seropositive rheumatoid art 2018 OBJECTIVES: Recent studies suggest that implementation of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) leads to higher inflammatory activity in seronegative compared with seropositive patients at time of diagnosis. Our aim was to compare the disease course in seronegative and seropositive patients classified according to the 2010 criteria. METHODS: DMARD-naïve patients with RA fulfilling the 2010 criteria were included in the treat-to-target ARCTIC trial and followed for 24 months. We stratified patients as seropositive (rheumatoid factor (RF)+, anticitrullinated protein antibodies (ACPA)+ or both) or seronegative (RF- and ACPA-) and compared disease activity, radiographic progression, treatment response and remission rates across groups. RESULTS: 230 patients were included with mean (SD) age 51.4 (13.7) years, and 61% were female. 34 patients (15%) were seronegative. At 24  months, disease activity measures, radiographic progression and remission rates were similar between groups, despite more inflammatory activity in seronegative patients at baseline. Treatment response was slower in seronegative compared with seropositive patients. The groups received similar treatment. CONCLUSION: Our findings suggest that among patients with RA classified according to the 2010 ACR/EULAR criteria, seronegative patients respond well to modern treatment strategies. However, treatment response was somewhat slower in seronegative patients and radiographic progression was similar in seronegative and seropositive patients. Our results indicate that seronegative RA is not a mild form of the disease and requires intensive treat-to-target therapy similar to treatment of seropositive RA.
30237625 Pharmacoeconomic evaluation of treatment effectiveness with selected biologic treatment in 2018 OBJECTIVES: Modern treatment of autoimmune diseases is becoming increasingly widely used. We owe it to the continuous and rapid development of biotechnology, molecular biology, immunology, and biochemistry. The proven effectiveness of biological therapy in rheumatoid arthritis (RA) should result in its widespread use. At present, only about 1% of patients with RA have access to biological therapy in Poland. MATERIAL AND METHODS: The study material was retrospectively collected in the Rheumatology and Systemic Tissue Diseases Clinic and Rheumatology Outpatient Clinic in dr Jan Biziel University Hospital No. 2 in Bydgoszcz 2009-2014. Patients were divided into 3 groups: patient receiving infliximab, etanercept and adalimumab. RESULTS: The study involved analyses of cost effectiveness. The time horizon of patient documentation analysis ranged from the time a patient was enrolled to infliximab, etanercept or adalimumab therapy until remission of the disease. The majority of patients achieved remission in the case of adalimumab treatment (85.29%), followed by etanercept (74.07%), then infliximab (37.21%). Taking into account the DAS28 parameter, analysis was performed using medical costs of the analyzed treatment regimens. For this purpose, the incremental cost-effectiveness ratio (ICER) was calculated. According to the analysis, obtaining one DAS28 unit, replacing infliximab with etanercept, would cost PLN 40 964 67. Higher costs would be required in the case of replacement of infliximab with adalimumab - PLN 43 076 08. Obtaining one additional DAS28 unit (in this case, a decrease in DAS28 by one unit) by introducing adalimumab instead of etanercept would amount to PLN 45 409 74. CONCLUSIONS: Undoubtedly, the pharmacoeconomic analysis makes it easier to decide on the appropriate treatment. Therefore, its implementation should be a widely used solution not only for RA, but also for other diseases. Health care and other entities' systems should also be improved in such a way that the data needed for pharmacoeconomic analysis are fully available.
29755555 The Ethanolic Extract of Eysenhardtia polystachya (Ort.) Sarg. Bark and Its Fractions Dela 2018 Winter Eysenhardtia polystachya is widely used in folk medicine as an anti-rheumatic and analgesic agent, but no systematic study of its effects on several markers associated with rheumatoid arthritis and its ethnomedical use as analgesic agent has been performed. We evaluated the anti-arthritic and antinociceptive properties of an ethanolic extract of E. polystachya (EE) bark and its rich-flavonoids fractions in murine models. The EE was administered orally at doses of 25, 50, 100, and 200 mg/kg/day, and its fractions at 25 mg/kg/day in all animal models. Anti-arthritic activity was evaluated using a complete Freund´s adjuvant (CFA)-induced rheumatoid arthritis model in rats. The severity of arthritis was evaluated by changes in paw oedema, body weight, arthritic index, radiological scores, histological assessment of synovial joints, erythrocyte sedimentation rate, haematocrit, haemoglobin, serum rheumatoid factor, serum C-reactive protein and serum levels of the pro-inflammatory cytokines IL-1β, IL-6, TNF-α, IL-18, IFN-γ, GM-CSF, and anti-inflammatory cytokines IL-4, IL-10, IL-13. Antinociceptive activity was evaluated using an acetic acid-induced abdominal contraction test and a hot-plate test in mice. EE and its rich-flavonoids fractions inhibited secondary inflammatory reactions, diminished the specific histopathological alterations in the joint capsule and reduced the serum concentrations of the pro-inflammatory cytokines IL-6, TNF-α, and GM-CSF in arthritic rats. EE also reduced the number of writhes produced by acetic acid and increased the response time on the hot plate for mice. Our findings support the use of Eysenhardtia polystachya bark for the treatment of rheumatoid arthritis and pain management.
32185295 Red Cell Distribution Width in Rheumatoid arthritis. 2018 Mar BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease, which affects the joints and other body systems. Red cell distribution width (RDW) is a part of the complete blood count (CBC) test and estimates erythrocytic variability. OBJECTIVE: To evaluate RDW in RA and to assess the relationships of baseline demographic and clinical characteristics with RDW. PATIENTS AND METHODS: A total of 111 patients with RA diagnosed according to the 2010 American College of Rheumatology/European League Against Rheumatism (2010 ACR/EULAR) classification criteria for Rheumatoid arthritis) and compared with 97 healthy individuals matched in age and gender as controls. Age, gender, body mass index (BMI), clinical diseases activity index (CDAI) and diseases activity score 28 using erythrocyte sedimentation rate (ESR) (DAS28-ESR), and diseases durations were recorded. Rheumatoid Factor (RF), anti-citrullinated peptide antibody (ACPA), complete blood count (CBC) and ESR were all measured. RESULTS: The mean age for patients and controls were 46.53 ± 11.89 and 48.19 ± 12.06 years respectively (p=0.321). RDW was significantly higher in patients (14.5 ± 2.8%) compared with controls (12.4 ± 1.1 %) (p=>0.001). There was no significant correlation between various variables (age, Body Mass Index [BMI], disease duration, CDAI), DAS28-ESR, ESR, gender, RF, and ACPA) with RDW. The RDW had good ability to differentiate RA patients from controls (AUC=0.804, 95% CI=0.744 - 0.856. p=<0.001), while ESR had excellent ability to differentiate between RA patients and controls (AUC=0.926, 95% CI=0.882 - 0.958, p<0.001). CONCLUSIONS: RDW was significantly elevated in RA patients.
29408684 A novel dexamethasone-loaded liposome alleviates rheumatoid arthritis in rats. 2018 Apr 5 In this study, an inflammation-targeted delivery system based on a liposomal carrier was developed to deliver hydrophobic dexamethasone against arthritis. Using two FDA-approved excipients for intravenous injection, dexamethasone loaded liposome (Dex-Lip) was prepared by a thin-film hydration method. The biodistribution of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine-loaded liposomes (DiD-Lips) were performed in rats with adjuvant-induced arthritis and demonstrated specific targeting efficacy in the disease site. DiD-Lips showed prolonged retention time in the inflammatory joint tissues compared with free DiD. Dex-Lips effectively suppressed the joint swelling in arthritis rats and significantly down-regulated serum pro-inflammatory cytokines including tumor necrosis factor-α and interleukin-1β when compared to free dexamethasone. Furthermore, Dex-Lips had no significantly impact on the body weight, alleviated the hyperglycemia and improved haematological profiles of rheumatoid arthritis rats during the treatment process. Taken together, a safe liposomal delivery system was developed to achieve inflammation targeted therapy against arthritis.
29515679 Role of Diet in Influencing Rheumatoid Arthritis Disease Activity. 2018 BACKGROUND: Patients with Rheumatoid Arthritis (RA) frequently ask their doctors about which diets to follow, and even in the absence of advice from their physicians, many patients are undertaking various dietary interventions. DISCUSSION: However, the role of dietary modifications in RA is not well understood. Several studies have tried to address these gaps in our understanding. Intestinal microbial modifications are being studied for the prevention and management of RA. Some benefits of vegan diet may be explained by antioxidant constituents, lactobacilli and fibre, and by potential changes in intestinal flora. Similarly, Mediterranean diet shows anti-inflammatory effects due to protective properties of omega-3 polyunsaturated fatty acids and vitamins, but also by influencing the gut microbiome. Gluten-free and elemental diets have been associated with some benefits in RA though the existing evidence is limited. Long-term intake of fish and other sources of long-chain polyunsaturated fatty acids are protective for development of RA. The benefits of fasting, anti-oxidant supplementation, flavanoids, and probiotics in RA are not clear. Vitamin D has been shown to influence autoimmunity and specifically decrease RA disease activity. The role of supplements such as fish oils and vitamin D should be explored in future trials to gain new insights in disease pathogenesis and develop RA-specific dietary recommendations. CONCLUSION: Specifically more research is needed to explore the association of diet and the gut microbiome and how this can influence RA disease activity.
29983983 Pulmonary lymphangitic carcinomatosis with ground-glass opacities as presentation of prost 2018 Oct There is a broad differential diagnosis for interstitial shadows on chest computed tomography in rheumatoid arthritis patients, especially those previously treated with immunosuppressant drugs. We report an immunocompromised rheumatoid arthritis patient in respiratory failure with diffuse ground-glass opacities (GGOs), who was diagnosed with pulmonary lymphangitic carcinomatosis as the initial presentation of prostate cancer. He was successfully treated with chemohormonal androgen deprivation therapy, including bicalutamide, leuprorelin acetate, denosumab, and docetaxel. Metastatic pulmonary lymphangitis, rarely from the prostate, should always be considered in the differential diagnosis of GGOs, even when the patient has no known prior malignancies.
30505369 Association Between STAT4 rs7574865 Polymorphism and Rheumatoid Arthritis: Debate Unresolv 2018 BACKGROUND: STAT4 rs7574865 polymorphism has been evidently associated with susceptibility to Rheumatoid Arthritis (RA) in European and Eastern Asian populations, whereas studies in other countries reported otherwise. OBJECTIVE: We investigated the distribution of STAT4 rs7574865 polymorphism in a group of Syrian RA patients. METHODS: Eighty-one RA patients and forty healthy controls were enrolled and STAT4 rs7574865 was genotyped by direct sequencing. RA patients were stratified according to Anti-Citrullinated Protein Antibodies (ACPA) status for analysis. RESULTS: Minor T allele frequencies were 30.4%, 16.7%, and 23.8% in ACPA-positive RA patients, ACPA-negative RA patients, and healthy controls, respectively. No significant differences in STAT4 rs7574865 allele/genotype frequencies were found between ACPA-positive RA patients, ACPA-negative RA patients, and healthy controls (P>0.05). CONCLUSION: STAT4 rs7574865 TT genotype showed a potential impact on ACPA positivity in Syrian RA patients. However, STAT4 rs7574865 effect on RA onset and severity is minor compared to other genetic factors such as HLA-DRB1 shared epitope alleles.
29997624 Ontology and Function of Fibroblast-Like and Macrophage-Like Synoviocytes: How Do They Tal 2018 Fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS) are the two main cellular components of the synovium. It has been widely reported that FLS and MLS play essential roles in the joint pathology of rheumatoid arthritis (RA). Although various studies have analyzed both human and animal tissues and have shown that both cell types are involved in different stages of RA, ontology, and specific functions of both cell populations and their interactions are not well understood. In this review, we will summarize recent research on FLS and MLS in RA and focus on the development and function of two predominant synovial cell types. In addition, we will discuss the communication between FLS or MLS and highlight potential treatments for RA that involve synoviocytes.
30207561 Effect of Ozone in Freund's Complete Adjuvant-Induced Arthritis. 2018 Jun OBJECTIVES: This study aims to investigate the effectiveness and reliability of ozone (O3) in Freund's complete adjuvant (FCA)-induced arthritis, an animal model for rheumatoid arthritis. PATIENTS AND METHODS: Thirty-six four- to five-month-old male Wistar rats weighing between 274-420 gr were used in this study. Saline was injected into the hind paws of half of these rats, and FCA was injected into the other half. At the end of two weeks, 40 μg of O3 was administered to nine rats from each group twice a week for seven total doses. The rats were followed-up in terms of clinical findings. At the sixth week, the rats were sacrificed and serum malondialdehyde, glutathione peroxidase, and superoxide dismutase levels were measured. In addition, ankle joints were separated for histopathological examination. RESULTS: Significant improvement was observed in terms of hind-paw diameter, severity of arthritis, and histopathological findings of inflammation after O3 treatment in the group with FCA-induced arthritis. Although it was not quite significant, an upward trend was detected in oxidative stress markers with O3 treatment. CONCLUSION: This study, the first to investigate the effects of systemic O3 on the clinical and histopathological outcomes of rheumatoid arthritis, indicates that O3 is a highly effective and reliable treatment method in FCA-induced arthritis in animal models.
29942363 The role of the JAK/STAT signal pathway in rheumatoid arthritis. 2018 Jun Proinflammatory cytokine activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway is a critical event in the pathogenesis and progression of rheumatoid arthritis. Under normal conditions, JAK/STAT signaling reflects the influence of negative regulators of JAK/STAT, exemplified by the suppressor of cytokine signaling and protein inhibitor of activated STAT. However, in rheumatoid arthritis (RA) both of these regulators are dysfunctional. Thus, continuous activation of JAK/STAT signaling in RA synovial joints results in the elevated level of matrix metalloproteinase gene expression, increased frequency of apoptotic chondrocytes and most prominently 'apoptosis resistance' in the inflamed synovial tissue. Tofacitinib, a JAK small molecule inhibitor, with selectivity for JAK2/JAK3 was approved by the United States Food and Drug Administration (US FDA) for the therapy of RA. Importantly, tofacitinib has demonstrated significant clinical efficacy for RA in the post-US FDA-approval surveillance period. Of note, the success of tofacitinib has spurred the development of JAK1, JAK2 and other JAK3-selective small molecule inhibitors, some of which have also entered the clinical setting, whereas other JAK inhibitors are currently being evaluated in RA clinical trials.
30207564 Bee Venom and Hesperidin Effectively Mitigate Complete Freund's Adjuvant-Induced Arthritis 2018 Jun OBJECTIVES: This study aims to assess the antirheumatic activity of bee venom (BV) and/or hesperidin as natural products in complete Freund's adjuvant (CFA)-induced arthritis in male Wistar rats. MATERIAL AND METHODS: Rheumatoid arthritis was induced in 30 male Wistar rats (weight 130 g to 150 g; age 10 to 12 weeks) by subcutaneous injection of CFA into the right hind paw of the rats. The rats were divided into five groups of six rats in each and administered the following regimens for 21 days: Normal group (given the equivalent volume of saline and carboxymethylcellulose), arthritic group (given the equivalent volume of saline and carboxymethylcellulose), arthritic group treated with BV (treated with BV along with carboxymethylcellulose), arthritic group treated with hesperidin (treated with hesperidin along with saline), and arthritic group treated with BV and hesperidin (treated with BV and hesperidin concurrently). RESULTS: Bee venom and/or hesperidin successfully reversed the CFA-arthritis-induced increases in right hind leg paw swelling, leukocytes' count, liver lipid peroxidation, serum inflammatory cytokine interleukin (IL-2 and IL-12) levels and spleen tumor necrosis factor-alpha messenger ribonucleic acid expression. Moreover, the CFA-induced down-regulation in serum IL-10 level and spleen IL-4 messenger ribonucleic acid expression as well as the deterioration in the antioxidant defense system were significantly improved as a result of BV and hesperidin administration. Both treatments also markedly counteracted the severe inflammatory changes and leukocytic infiltration in the periarticular tissue of the ankle joints. In addition, BV and hesperidin obviously amended the lymphoid hyperplasia in white pulps of spleen as well as the widening of the medulla and mononuclear cell infiltration found in thymus. CONCLUSION: Bee venom and hesperidin administration produced their ameliorative effects on rheumatoid arthritis via their antioxidant, antiinflammatory and immunomodulatory potentials. BV plus hesperidin particularly seemed to be the most potent in improving rheumatoid arthritis in Wistar rats.