Carbohydrate-deficient transferrin depends on disease activity in rheumatoid arthritis and systemic sclerosis.

OBJECTIVES: Changes in the glycosylation of plasma proteins have been linked to the aetiology of the rheumatic diseases. The aim of this study was to determine and compare the levels of carbohydrate-deficient transferrin (CDT) in patients with rheumatoid arthritis (RA), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE). METHOD: Studies were carried out in 29 female patients with RA, 27 with SSc, and 17 with SLE. CDT was assayed by the N Latex CDT immunonephelometric assay. RESULTS: The levels of %CDT in the sera of RA, SLE, and SSc patients were significantly higher than in controls while the absolute concentrations of CDT were unchanged. %CDT, CDT, and transferrin do not differ significantly between patients with rheumatic diseases. In RA and SSc patients, a positive correlation was observed between %CDT and C-reactive protein (CRP), as well as a positive correlation in RA patients between %CDT and 28-joint Disease Activity Score (DAS28). CONCLUSIONS: The changes in the serum %CDT concentration in patients with RA and SSc correlated with disease activity markers.

Evaluation of skin thickness lesions in patients with Lyme disease measured by modified Rodnan total skin score.

Recently, a possible etiological connection between infection with Borrelia burgdorferi and various skin lesions, including morphea and systemic sclerosis (SSc), has been discussed. The aim of our study was the evaluation of frequency of skin thickening typical of SSc or morphea in the group of patients with Lyme disease (LD) with frequent exposition to tick bites. The group consisted of 110 patients with LD frequently exposed to tick bites form the northeastern Poland, which is an endemic area for this disease. To measure the skin lesions, the modified Rodnan total skin score (RTSS) was used. In the analyzed group, no skin changes typical of morphea or skin thickening were found. According to RTSS, all patients scored 0 points. Raynaud's phenomenon in all patients was not found. The relationship between scleroderma or morphea and LD is still a matter of controversy. Described by some authors, cases with LD and scleroderma may be associated with co-existence of B. burgdorferi infection with autoimmune process.

Relationship between CDT and disease activity in rheumatoid arthritis.

The aim of this study was to estimate the serum concentration of carbohydrate-deficient transferrin (CDT) in patients with rheumatoid arthritis (RA) and the relationship between the CDT level and disease activity in RA patients. Studies were carried out in 47 female patients with RA and 32 healthy women. Disease activity of RA was evaluated using the 28-joint count Disease Activity Score (DAS 28). Serum CDT was determined by particle-enhanced immunononephelometry using the N Latex CDT test. Patients with RA had significantly lower serum concentrations of CDT compared with controls. The correlation study showed the significant negative relationship between CDT and DAS 28 (r = - 0.483, p = 0.011). There were no correlations between serum CDT level and patient's age, disease duration, number of tender and swollen joints, and degree of disability evaluated by the Health Assessment Questionnaire. The level of CDT in patients with RA was significantly decreased and confirms the changes in transferrin glycosylation which are dependent on the disease activity. Therefore, measurement of CDT in the sera of patients with RA can be useful for the evaluation of disease activity in these patients.

Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres.

OBJECTIVE: Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate in other patients, especially from other centres or countries. A study was undertaken to validate the prognostic model to predict 5-year survival in SSc in other centres throughout Europe. METHODS: A European multicentre cohort of patients with SSc diagnosed before 2002 was established. Patients with SSc according to the preliminary American College of Rheumatology classification criteria were eligible for the study when they were followed for at least 5 years or shorter if they died. The primary outcome was 5-year survival after diagnosis of SSc. The predefined prognostic model uses the following baseline variables: age, gender, presence of urine protein, erythrocyte sedimentation rate (ESR) and carbon monoxide diffusing capacity (DLCO). RESULTS: Data were available for 1049 patients, 119 (11%) of whom died within 5 years after diagnosis. Of the patients, 85% were female, the mean (SD) age at diagnosis was 50 (14) years and 30% were classified as having diffuse cutaneous SSc. The prognostic model with age (OR 1.03), male gender (OR 1.93), urine protein (OR 2.29), elevated ESR (1.89) and low DLCO (OR 1.94) had an area under the receiver operating characteristic curve of 0.78. Death occurred in 12 (2.2%) of 509 patients with no risk factors, 45 (13%) of 349 patients with one risk factor, 55 (33%) of 168 patients with two risk factors and 7 (30%) of 23 patients with three risk factors. CONCLUSION: A simple prognostic model using three disease factors to predict 5-year survival at diagnosis in SSc showed reasonable performance upon validation in a European multicentre study.

Morning symptoms in rheumatoid arthritis: a defining characteristic and marker of active disease.

Many human biological processes are regulated by circadian rhythms, which follow 24-h cycles and involve the neuroendocrine and immune systems. Pathological manifestations of this system may also follow circadian rhythms. In rheumatoid arthritis (RA), clinical symptoms of joint stiffness, pain, and functional disability are commonly most severe in the early morning. These symptoms closely follow the circadian rhythm of the pro-inflammatory cytokine, interleukin (IL)-6. In RA, the increase in nocturnal anti-inflammatory cortisol secretion is insufficient to suppress ongoing inflammation, resulting in the morning symptoms characteristic of RA. Established diagnostic criteria for RA include morning stiffness, although it is not part of the more recent classification criteria developed to guide early treatment decisions. Measures that are widely used to monitor disease control also omit morning stiffness. However, such measures may not capture all disease activity, and one in six patients in remission or with low disease activity still experiences prolonged morning stiffness. Such findings suggest that morning symptoms in RA remain an important marker of active disease that should continue to be monitored.

Smokers and non smokers with rheumatoid arthritis have similar clinical status: data from the multinational QUEST-RA database.

OBJECTIVES: To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. METHODS: The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures. RESULTS: Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). CONCLUSIONS: RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database.

OBJECTIVE: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. METHODS: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. RESULTS: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. CONCLUSIONS: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

Effect of etanercept on serum levels of soluble cell adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor in patients with rheumatoid arthritis.

OBJECTIVE: Endothelium and adhesion molecules are engaged in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to analyse the effect of etanercept on the levels of soluble cell adhesion molecules (sCAMs) and vascular endothelial growth factor (VEGF) in patients with active RA. METHODS: Patients were receiving 50 mg/week of subcutaneous etanercept and 10-25 mg/week of methotrexate (MTX). Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and VEGF were measured by enzyme-linked immunosorbent assay (ELISA) in 18 RA patients (prior to injection) at 0, 3, 6, 9, and 12 months. RESULTS: A decrease in serum levels of sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01), and VEGF (p<0.001) was observed in RA patients after 3 months of treatment with etanercept. Six months of therapy with etanercept prolonged the suppression of serum sICAM-1 (p<0.01) and even more remarkably diminished sVCAM-1, sE-selectin, and VEGF (in all cases p<0.001) concentrations as compared to baseline (month 0). Treatment also effectively diminished sICAM-1, sVCAM-1, and VEGF levels at months 9 and 12 (in all cases p<0.001), and less significantly sE-selectin (p<0.05 at month 9 and p<0.01 at month 12). The Disease Activity Score including a 28-joint count (DAS28) measured at 3, 6, 9, and 12 months decreased significantly compared to baseline (in all cases p<0.001). CONCLUSION: Our study shows that, besides a rapid suppression of disease activity, serum sCAM and VEGF concentrations are downregulated following anti-tumour necrosis factor alpha (TNFalpha) therapy combined with MTX. Prolonged treatment with etanercept sustained or even more remarkably diminished the sCAM and VEGF serum concentrations.

Clinical significance of nailfold capillaroscopy in systemic lupus erythematosus: correlation with endothelial cell activation markers and disease activity.

OBJECTIVE: To evaluate whether nailfold capillaroscopy (NC) changes are associated with the main serum endothelial cell activation markers and the disease activity of systemic lupus erythematosus (SLE). METHODS: Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble E-selectin (sE-selectin), and soluble thrombomodulin (sTM) were determined by an enzyme-linked immunosorbent assay (ELISA) in 80 SLE patients and 33 healthy controls. RESULTS: Nailfold capillary abnormalities were seen in 74 out of 80 (92.5%) SLE patients. A normal capillaroscopic pattern or mild changes were found in 33 (41.25%) and moderate/severe abnormalities in 47 (58.75%) of all SLE patients. In SLE patients a capillaroscopic score >1 was more frequently associated with the presence of internal organ involvement (p < 0.001) as well as with immunosuppressive therapy (p < 0.01). Significant differences were found in VEGF (p < 0.001), ET-1 (p < 0.001), sE-selectin (p < 0.01), and sTM (p < 0.001) serum concentrations between SLE patients with a capillaroscopic score > 1 and controls. SLE patients with severe/moderate capillaroscopic abnormalities showed significantly higher VEGF serum levels than patients with mild changes (p < 0.001). Moreover, there was a significant positive correlation between the severity of capillaroscopic changes and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p < 0.005) as well as between capillaroscopic score and VEGF serum levels (p < 0.001). CONCLUSIONS: Our findings confirm the usefulness of NC as a non-invasive technique for the evaluation of microvascular involvement in SLE patients. A relationship between changes in NC, endothelial cell activation markers and clinical features of SLE suggest an important role for microvascular abnormalities in clinical manifestation of the disease.

Mechanism of action of glucocorticosteroids. Inhibition of T cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B4.

The mechanism whereby glucocorticosteroids are immunosuppressive is unknown. One potential mechanism of action of these compounds is inhibition of arachidonic acid metabolism. We found that the inhibition of lymphocyte proliferation by hydrocortisone or dexamethasone was mimicked by nonspecific lipoxygenase inhibitors and also by a specific 5-lipoxygenase inhibitor, but not by a specific cyclooxygenase inhibitor. Mitogen-stimulated cultures of T cells produce approximately 5 X 10(-9) M leukotriene B4 (LTB4) in 24 h. This production of LTB4 is completely inhibited by concentrations of hydrocortisone or lipoxygenase inhibitors that inhibit mitogen-induced [3H]thymidine incorporation. The inhibition of lymphocyte proliferation by either hydrocortisone or by the 5-lipoxygenase inhibitor was totally reversed by LTB4 but not by leukotriene C4 or leukotriene D4. LTB4 had no effect on the inhibition of lymphocyte proliferation by noncorticosteroids such as prostaglandin E2, histamine, or gamma-interferon. The inhibition of interleukin 2 (IL-2) production by hydrocortisone or dexamethasone was also completely reversed by exogenous LTB4. LTB4 alone did not cause IL-2 production or cell proliferation when added to resting lymphocytes. Thus, endogenous LTB4 production appears to be necessary but not sufficient for phytohemagglutinin-induced IL-2 production and lymphocyte proliferation. Glucocorticosteroids inhibit IL-2 production and lymphocyte proliferation by inhibiting endogenous LTB4 production.

Regulation of serum chemokines following infliximab therapy in patients with rheumatoid arthritis.

OBJECTIVE: We studied the effects of the multiple infusions of infliximab, a chimeric anti-tumor necrosis factor alpha (anti-TNF-alpha) antibody, on the serum chemokines levels in patients with active rheumatoid arthritis (RA). METHODS: RA patients were supposed to receive 9 infusions of infliximab (3mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter with the same dose. All patients continued treatment with methotrexate (MTX) (7.5-20mg/week). Serum concentrations of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA at weeks 0, 2, 6, 14, 38, prior to infusion, and additionally at week 62. RESULTS: Initial infusion of infliximab caused reduction in serum IL-8, RANTES and MCP-1 (in all cases p < 0.001) levels. Subsequent infliximab administrations also significantly decreased serum chemokines levels, but was less effective. Prior to the first infliximab infusion serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) or CRP levels, number of swollen joints and disease activity score (DAS). Following next drug infusions such associations were far less significant. Infliximab treatment induced a significant reduction in the number of monocytes observed through the whole study (in all cases p < 0.05). CONCLUSION: Anti-TNF-alpha antibody therapy accompanied by MTX, beside a rapid clinical improvement, reduced serum chemokines concentrations in RA patients. Subsequent administrations of infliximab sustained chemokines decrease, although to a lesser extent than the first two dose of infliximab.

Activity of N-acetyl-beta-hexosaminidase and its isoenzymes in serum and synovial fluid from patients with different arthropathies.

OBJECTIVE: To evaluate the activity of N-acetyl-Beta-hexosaminidase (HEX) and its isoenzymes in the serum and synovial fluid of healthy volunteers and patients with an injury to the anterior cruciate ligament and/or meniscus (ACL) osteoarthritis (OA), juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA). METHODS: The activity of HEX and its isoenzymes was determined according to Zwierz et al. method. Protein content was determined by the biuret method. RESULTS: The specific activity of HEX and its isoenzymes in the serum of patients with JIA showed a tendency to increase in comparison to the reference group. The specific activity of total HEX in the serum of RA patients was significantly increased in comparison to control. Our results show, that specific activity of HEX in synovial fluid, in the reference group 4.2 +/- 0.21 microkat/kg protein (0.25 unit/mg protein), is similar to activity in normal temporomandibular joint fluid (0.3 unit/mg protein). Therefore, we included this group in our research. In patients with OA and ACL injuries, HEX and its isoenzymes showed a tendency to increase in the specific activity in synovial fluid. The specific activity of HEX and its isoenzymes in the synovial fluid of patients with RA and JIA was significantly elevated in comparison to the control and the remaining groups. CONCLUSION: In the synovial fluid of patients with JIA and RA, the specific activity of HEX and its isoenzymes significantly increased in comparison to control and patients with diseases of a non-inflammatory etiology (OA and ACL). In the synovial fluid of control and diseased groups, HEX constituted a higher percent of total proteins than in serum.

Jacques Forestier's vanished bowstring sign in ankylosing spondylitis: a call to test its validity and possible relation to spinal myofascial hypertonicity.

Jacques Forestier's bowstring sign (signe de la "corde de l'arc") in ankylosing spondylitis (AS) was described by him in his 1951 book (French). In free lateral bending, the early AS patient has palpably firm, contracted dorsolumbar muscles on the concave side, opposite to the findings in normals. Forestier described this sign as a common and characteristic finding in AS. Perplexingly, the sign is essentially unknown in the rheumatologic field. A single report (Polish) on electromyographic (EMG) findings in AS and control subjects documented the electromotor component of the bowstring sign as well as its diagnostic utility in early AS patients. In this paper, the literature on EMG studies in series of AS patients is reviewed as well as kinesiologic EMG studies of normals in lateral bending. Paravertebral and other muscle pathology in AS was reviewed in relation to the EMG findings. Critical, controlled assessment of Forestier's bowstring sign and biomechanical investigations of the dorsolumbar muscles in AS promise to offer new insights into the early physiopathogenesis of this unique disease.

Interleukin-6, soluble interleukin-2 receptor and soluble interleukin-6 receptor in the sera of patients with different histological patterns of rheumatoid synovitis.

OBJECTIVE: The present study was conducted to investigate whether the serum levels of interleukin 6 (IL-6), soluble IL-2 receptor (sIL-2R) and sIL-6R are associated with the morphological appearance of rheumatoid arthritis (RA). METHODS: Using the ELISA technique we measured the IL-6, sIL-2R and sIL-6R concentrations in the serum of 34 patients with RA and 28 patients with osteoarthritis (OA). Histological analysis of synovial samples distinguished 2 types of rheumatoid synovitis. Twenty-one RA specimens presented diffuse infiltrates of mononuclear cells without any specific microanatomical organization. In remaining 13 samples the formation of lymphocytic follicles with germinal center-like structures was found. RESULTS: Serum levels of IL-6, sIL-2R and sIL-6R were elevated in patients with RA compared to the OA control group (p < 0.001, p < 0.001 and p < 0.05 respectively). Concentrations of IL-6 and sIL-2R were highest in the serum of RA patients with follicular synovitis in comparison to patients with diffuse synovitis (p < 0.001 and p < 0.01 respectively) and could distinguish RA patients with these two histological variants of the disease. Serum levels of IL-6 and sIL-2R correlated with markers of disease activity such as ESR and CRP levels. In addition, the clinical data suggest a more severe disease among RA patients with follicular synovitis. CONCLUSION: Distinct histological types of rheumatoid synovitis associated with unique serum concentrations of IL-6 and sIL-2R reflect levels of disease activity and confirm the concept of RA heterogeneity.

Serum autoantibodies profile and increased levels of circulating intercellular adhesion molecule-1: a reflection of the immunologically mediated systemic vasculopathy in rheumatic diseases?

The clinical manifestation of systemic vasculitis may be postulated as a consequence of immune response abnormalities in the course of connective tissue diseases (CTD). The aim of this study was to elucidate the significance of the different autoantibodies and soluble intercellular adhesion molecule 1 (sICAM-1) being shed into the circulation in the diagnosis of vasculitis in rheumatic diseases. Sera of 86 patients with rheumatic diseases (54 with rheumatoid arthritis (RA) and 32 with CTD) were analyzed for the concentrations of sICAM-1 levels by the enzyme-linked immunosorbent assay (ELISA). Control sera were obtained from 30 healthy individuals. Anti-nuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA) antibodies and anti-proteinase 3 (PR-3) antibodies (cytoplasmic specific anti-neutrophil cytoplasmic autoantibodies, cANCA) were assessed by the ELISA method. Fifty out of the 86 patients had systemic lesions. A pathological picture of the vascular loop under nailfold capillary microscopy was found in 84 patients. In 19 patients the microvascular changes were advanced, in 35 moderate and in 30 mild. All patients with articular manifestations had pathological changes under capillary microscopy. Patients with advanced changes under capillary microscopy had longer disease durations than patients with a mild intensity of vasculitis. The serum concentrations of sICAM-1 were significantly increased in RA and CTD patients compared with 30 controls (in both cases p<0.001). Moreover, RA and CTD patients with systemic vasculitis showed significantly higher levels of sICAM-1 than those without vascular involvement (p<0.001 and p<0.005 respectively). ANA were observed in significantly elevated concentration among RA and CTD patients with the systemic damage compared with patients without organ injury (p<0.001 and p<0.05 respectively). Also, cANCA levels were two-fold higher, but only among CTD patients with systemic damage (p<0.05). Serum concentrations of sICAM-1 were elevated in the patients showing the presence of ANA antibodies (p<0.05). Significant correlations between ANA level and disease duration and hemoglobin concentration were observed. The concentrations of cANCA correlated with those of rheumatoid factor and of dsDNA with patient age. We conclude that systemic lesions in the course of RA and CTD are accompanied by the microvascular injury observed under nailfold capillary microscopy. Our data suggest that sICAM-1, ANA and cANCA serum levels may reflect the extent of the vascular involvement in RA and CTD patients.

Decreased activity of interleukin-2 inhibitor in plasma of patients with systemic lupus erythematosus.

Low levels of plasma interleukin-2 inhibitory activity were found in patients with systemic lupus erythematosus (SLE) compared to normal individuals. The depression of the inhibitory activity was significant in patients with severe and moderate SLE while only a slight decrease was observed in the mild form of the disease.

Interleukin-1-production by monocytes from patients with systemic lupus erythematosus.

Production of interleukin-1 (IL-1) by glass-adherent monocytes from 18 patients with systemic lupus erythematosus (SLE) was measured. Patients were divided into three groups according to disease activity. A deficient production of IL-1 was found in monocytes of SLE patients both without stimulation and after stimulation with 5 micrograms of lipopolysaccharide. The decreased production correlated with the degree of disease. Addition of phorbol myristate acetate to monocytes caused only partial normalization of the decreased IL-1 production. The IL-1 deficiency in SLE is postulated to be a part of complex abnormalities of cell-mediated immunity in this disease.

[Guillain-Barré syndrome in a patient with primary sicca syndrome]. / Ciezki zespól Guillain-Barré u chorej z pierwotnym zespolem suchosci.

At the age of 23 the patient showed the first signs of dryness syndrome. Those symptoms developed progressively and during a few years primary Sjögren syndrome was noted. In the 37th year of life suddenly the patient developed very severe Gullian-Barré syndrome with involvement of the peripheral and central nervous system and with a considerable autonomic component. After treatment the patient improved, however mild symptoms of central and peripheral nervous system destruction remained. Those symptoms are still present and the patient is under the care of the Neurology and Rheumatology Clinic.

[Cytokines in rheumatoid arthritis. I. Proinflammatory cytokines]. / Cytokiny w reumatoidalnym zapaleniu stawów. I. Cytokiny prozapalne.

Proinflammatory cytokines play an important role in the pathogenesis of rheumatoid arthritis. It is why they became the targets for new therapies. In this review we describe their expression in synovial tissue, synovial fluid and in serum, and correlation with disease activity. Particular attention was paid to the possibilities of the alternative treatment strategies modifying the balance of cytokine network, in the rheumatoid arthritis patients, towards limiting their proinflammatory activity. Inhibiting the action of proinflammatory cytokines by using their specific inhibitors or anti-inflammatory cytokines have shown significant clinical benefits with mild side effects.

[Cytokines in rheumatoid arthritis. II. Anti-inflammatory cytokines]. / Cytokiny w reumatoidalnym zapaleniu stawów. II. Cytokiny przeciwzapalne.

In this review the role of anti-inflammatory cytokines in the pathogenesis of rheumatoid arthritis is presented. We describe their expression in synovial tissue, synovial fluid and in serum and correlation with disease activity. Special attention was paid to the possibilities of the alternative therapies modifying the balance of cytokine network, in the rheumatoid arthritis patients, towards anti-inflammatory state. Several such approaches have shown significant clinical benefits with mild side effects.