Endothelial dysfunction in Graves' disease.

PURPOSE: Graves' disease (GD) is an organ-specific autoimmune thyroid disease, characterized by hyperthyroidism due to excessive production of thyroid hormone induced by thyrotropin receptor-specific stimulatory autoantibodies. In this study, we determined serum levels of the soluble forms of ICAM-1, VCAM-1, vWF, IL-6, IL-12, IL-18, fibrinogen and CRP in patients with subclinical (SH) and overt hyperthyroidism (OH) caused by GD to elucidate a possible role of those parameters as markers of endothelium dysfunction (ED). MATERIAL/METHODS: The study included 96 patients: 52 with GD and 44 euthyroid controls, divided into 3 groups according to their thyroid function tests: SH, OH and controls (CG). RESULTS: The values of IL-6, IL-12 and IL-18 were significantly higher in GD than in CG patients (p < 0.0001, p < 0.0001; p < 0.00001, respectively). Significant difference of sVCAM-1 values were found in the patients with GD compared to CG (p < 0.0001). Patients with GD had significantly higher levels of PAI-1 (p < 0.00001), vWF (p < 0.0001), fibrinogen (p < 0.0001) in comparison to CG. In patients with OH, we observed statistically higher values of fibrinogen compared to SH group (p < 0.05). There were no significant differences in serum concentration of other study parameters in patients with SH compared to the OH. CONCLUSIONS: ED occurs during subclinical and overt hyperthyroidism causing decreased fibrinolytic activity, hypercoagulability and increased levels of IL-6, Il-12 and IL-18. These results support the notion that serum cytokines could be used as a marker of GD activity. Results of this study support the opinion that GD might require treatment as early as in the phase of SH.

A presumptive case of cerebral babesiosis in a dog in Poland caused by a virulent Babesia canis strain.

The aim of this paper was to present the first case of cerebral canine babesiosis due to infection by Babesia canis in a dog in Poland. A 5-year-old American Staffordshire Terrier was presented with an unusual clinical manifestation of acute babesiosis that included neurological signs and pancytopenia. Despite treatment the dog died. Diagnosis was based on microscopic examination of Giemsa-stained blood smears (detection of piroplasms in red blood cells) and post mortem examination of the brain by histopathology and PCR method. The amplified segment of the Babesia 18S RNA gene was sequenced. This enabled to determine that the cause of the disease had been the strain 18S RNA-B EU622793. This is one of two B. canis strains found endemically in Poland, which reveals a greater virulence than the strain 18S RNA-A EU622792. The described case indicates that this form of canine babesiosis should be taken into account in differential diagnosis in dogs exhibiting neurological symptoms, especially in the tick activity season.

The identification of Anaplasma spp. isolated from fallow deer (Dama dama) on a free-range farm in eastern Poland.

The aim of the present study was to investigate the occurrence of Anaplasma spp. in group of 50 fallow deer (Dama dama) from free-range farm in eastern Poland and determine what species of Anaplasma could infect these animals based on PCR gene sequencing. The PCR technique revealed the presence of 16S RNA Anaplasma spp. genetic material in the blood of 7 out of 50 examined animals. The sequences of the PCR products obtained showed a 100% homology with each other and 100% homology with GU 183908 sequence of A. phagocytophilum, isolated in our earlier study from a horse with clinical form of anaplasmosis. Here, we report the first molecular evidence of Anaplasma spp. among naturally infected fallow deer in eastern Poland.

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.

Soluble cell adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) in patients with early rheumatoid arthritis.

OBJECTIVE: The aim of the study was to analyse serum concentrations of soluble cell adhesion molecules (CAMs) in patients with early rheumatoid arthritis (RA) before and after 6 months of treatment with methotrexate (MTX). METHODS: We studied 32 RA patients, untreated with disease-modifying anti-rheumatic drugs (DMARDs) or corticosteroids, with disease duration less than 3 years. Twenty osteoarthritis (OA) patients constituted the control group. The analysis of serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin (sE-selectin) was based on a quantitative sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: In comparison with OA patients, higher serum concentrations of sICAM-1 (p<0.01), sVCAM-1 (p<0.01), and sE-selectin (p<0.05) were observed in untreated patients with early RA. Six months of treatment with MTX down-regulated serum concentrations of sICAM-1, sVCAM-1, and sE-selectin (in all cases p<0.001) in the RA patients studied. MTX treatment was also followed by a decrease in the clinical markers of RA activity, such as the number of painful and swollen joints, erythrocyte sedimentation rate (ESR), disease activity score (DAS), and C-reactive protein (CRP) levels. CONCLUSIONS: Patients with early RA are characterized by high serum concentrations of sICAM-1, sVCAM-1, and sE-selectin. Therapy with MTX resulted in clinical improvement and diminished serum levels of soluble CAMs in the RA patients studied, confirming the effectiveness of MTX in early stages of the disease.

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.

Kidney crisis in systemic sclerosis.

Renal crisis in systemic sclerosis occurs in the group of patients with rapid and aggressive course of the disease, often after several years of the ailment and with the diffuse form. Scleroderma renal crisis (SRC) is most frequently characterized by malignant hypertension, renal insufficiency, and less often by the symptoms of microangiopathic hemolytic anemia. Renal crisis symptoms appear suddenly and are not usually preceded by significant prodromal symptoms. SRC is always life-threatening and requires specific treatment with drugs blocking angiotensin-converting enzyme. Early diagnosis and introducing appropriate treatment give a patient a chance to survive SRC episode and improve his prognosis. SRC is of great importance to clinicians as it still causes high mortality rate. Chronic and subacute renal crisis is connected with a small risk of acute renal failure. However, it gradually leads to a substantial dysfunction of this organ. Thus, a useful examination in the diagnostics of chronic renal crisis is checking the vascular flow in renal cortex and evaluating intrarenal resistance.

The prevalence and management of hyperglycaemia in patients with rheumatoid arthritis on corticosteroid therapy.

BACKGROUND AND AIMS: Corticosteroids are commonly used in the treatment of RA. Hyperglycaemia resulting from corticosteroid use can lead to problems, particularly in those with impaired glucose tolerance and diabetes mellitus. We have examined how rheumatology clinics monitored and managed hyperglycaemia at base line and during treatment of patients with rheumatoid arthritis on corticosteroids. METHODS: Case notes of 102 patients with established RA, on long-term steroids were reviewed. We recorded a) blood glucose level at base line and whilst on steroids b) when and whether hyperglycaemia was addressed. RESULTS: There were 24 males and 78 females, with mean age of 62 +/- 15 years. Patients were on corticosteroids for a median duration of 24 months. Seventy-five per cent of patients were treated with oral prednisolone, the rest, except one patient on deflazacort, were on methylprednisolone. Blood glucose was measured at baseline in 97% of patients with 37% and 38% being monitored at three months and six months respectively and 36% annually thereafter. Nine patients (8.8%) developed diabetes mellitus during treatment, but one patient was detected and managed. There were six patients with existing diabetes mellitus in whom glycaemic control worsened between three to six months, but only one patient had treatment adjusted. CONCLUSIONS AND RECOMMENDATIONS: Physicians need to be aware that corticosteroids can increase blood glucose, worsen pre-existing diabetes and predispose to diabetes mellitus. Patients on long-term corticosteroids should be monitored at regular intervals as corticosteroid induced glycaemic excursions may lead to the development of diabetes mellitus and increased coronary risk.

Influence of doxycycline on the epiphyseal plate cartilage of the rats in experimental osteoarthrosis, induced by iodoacetate.

In 36 Wistar rats with the iodoacetate-induced experimental osteoarthrosis (OA), effects of doxycycline, given orally, were determined on histochemical reactions of glycosaminoglycans (GAG) in the epiphyseal plate cartilage. The epiphyseal plate of rats with OA was reduced in height (especially the proliferative zone), cell columns were disorganized, many chondrocytes were irregular and polygonal, their nuclei were pycnotic, the intensity of GAG staining was irregular and predominantly reduced, which can be interpreted as signs of degeneration. A concomitant administration of doxycycline in the second group of rats prevented, to some extent, the negative effects of iodoacetate on chondrocytes and led to a more pronounced intensity of GAG reactions in the matrix of the epiphyseal plate.

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.

Circulating tumour necrosis factor alpha and soluble tumour necrosis factor receptors in patients with different patterns of rheumatoid synovitis.

OBJECTIVE: To examine the relation between the serum levels of tumour necrosis factor alpha (TNFalpha), soluble tumour necrosis factor receptors (sTNF-R), and the histological pattern of rheumatoid synovitis. METHODS: An enzyme linked immunosorbent assay (ELISA) was used to measure TNFalpha, p55 sTNF-R, and p75 sTNF-R concentrations in the serum of 43 patients with rheumatoid arthritis (RA) and 34 patients with osteoarthritis (OA). RESULTS: Upon histological analysis two variants of rheumatoid synovitis emerged. Twenty six RA specimens presented only diffuse infiltrates of mononuclear cells. In the remaining 17 samples the formation of lymphocytic follicles with germinal centre-like structures was found. Serum concentrations of TNFalpha, p55 and p75 sTNF-R were raised in patients with RA compared with the OA control group (p<0.001 for all comparisons). Levels of TNFalpha, p55 and p75 sTNF-R were higher in the serum of patients with RA with follicular synovitis than in patients with diffuse synovitis (p<0.001, p<0.01, and p<0.05, respectively). Serum concentrations of TNFalpha, p55 and p75 sTNF-R correlated with markers of disease activity. CONCLUSION: Different histological types of rheumatoid synovitis associated with distinct serum levels of TNFalpha and sTNF-R reflect varying clinical activity of the disease and support the concept of RA heterogeneity.

Soluble adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and vascular endothelial growth factor (VEGF) in patients with distinct variants of rheumatoid synovitis.

BACKGROUND: Cell adhesion molecules and endothelial growth factors have an important role in the infiltrating of rheumatoid synovium with mononuclear cells, leading to the initiation and progression of the disease. OBJECTIVE: To investigate whether the serum profile of soluble adhesion molecules and of vascular endothelial growth factor (VEGF) is associated with the histological appearance of rheumatoid arthritis (RA). METHODS: Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and VEGF were assessed by enzyme linked immunosorbent assay (ELISA) in 40 patients with RA and 32 patients with osteoarthritis (OA). RESULTS: Histological analysis of synovium specimens distinguished two types of rheumatoid synovitis. Twenty four RA samples presented diffuse infiltrates of mononuclear cells without any further microanatomical organisation, whereas in the remaining 16 samples lymphocytic follicles with germinal centre-like structures were identified. In comparison with patients with OA, constituting a control group, higher serum concentrations of sICAM-1 (p<0.001), sVCAM-1 (p<0.001), sE-selectin (p<0.01), and VEGF (p<0.001) were detected in patients with RA. Raised concentrations of sICAM-1, sVCAM-1, and VEGF dominated in the serum of patients with RA with follicular synovitis compared with those with diffuse synovitis (p<0.01 for all comparisons). The serum concentrations of sICAM-1, sVCAM-1, and VEGF correlated with markers of disease activity such as the erythrocyte sedimentation rate and C reactive protein levels. Furthermore, the clinical data analysed in our study indicated that patients with RA with follicular synovitis tend to have more severe disease. CONCLUSIONS: The distinct histological appearances of rheumatoid synovitis associated with different serum profiles of sICAM-1, sVCAM-1, and VEGF reflect varied clinical activity of the disease and confirm RA heterogeneity. Patients with different histological forms of synovitis may respond differently to the treatment regimens.

Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in different histological variants of rheumatoid synovitis.

OBJECTIVE: Rheumatoid synovitis is characterized by an invasive and tissue-destructive infiltrate of lymphocytes, macrophages and synoviocytes. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) produced by these cells are important in the remodelling of the articular tissues in rheumatoid arthritis (RA). The aim of this study was to explore whether the serum concentrations of MMPs and their inhibitors were correlated with the histological appearance of the disease. METHODS: Tissue and serum samples were obtained from 37 patients with clinically active RA and 30 with osteoarthritis (OA). Morphological analysis allowed the division of RA synovial specimens into two distinct types. In 22 samples only diffuse infiltrates of mononuclear cells without further microanatomical organization were found. In 15 specimens we observed lymphocytic conglomerates with germinal centre-like structures. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1 and TIMP-2 were measured with an ELISA technique. RESULTS: Unique serum profiles of MMPs and TIMPs were identified in each of the two histological types of RA synovitis. The serum concentrations of MMP-1, MMP-3 and MMP-9 were higher in RA patients than in OA patients used as a control group (P<0.001 for all comparisons). These three MMPs dominated in the serum of RA patients with follicular synovitis compared with those with diffuse synovitis (P<0.05, P<0.01 and P<0.001 respectively). The analysis of the serum concentrations of TIMP-1 and TIMP-2 showed that their levels were also elevated in RA patients compared with OA patients (P<0.001 and P<0.01 respectively). Only TIMP-1 was found in a significantly higher concentration in the serum of RA patients with follicular synovitis than in those with diffuse synovitis (P<0.05). The serum concentrations of MMPs and TIMP-1 clearly identified patients with two different histological types of rheumatoid synovitis and with OA. Additionally, the analysis of clinical data showed that the rheumatoid disease in patients with follicular synovitis seemed to be more active than in those with diffuse synovitis. CONCLUSION: The morphological appearance of rheumatoid synovitis and the serum MMP and TIMP-1 profile were correlated with the clinical activity of the disease, confirming the heterogeneity of RA. These associations also suggest that patients with different histological forms of RA might require different treatment regimens.

T cell activation in rheumatoid synovium is B cell dependent.

Rheumatoid arthritis results from a T cell-driven inflammation in the synovial membrane that is frequently associated with the formation of tertiary lymphoid structures. The significance of this extranodal lymphoid neogenesis is unknown. Microdissection was used to isolate CD4 T cells residing in synovial tissue T cell/B cell follicles. CD4 T cells with identical TCR sequences were represented in independent, nonadjacent follicles, suggesting recognition of the same Ag in different germinal centers. When adoptively transferred into rheumatoid arthritis synovium-SCID mouse chimeras, these CD4 T cell clones enhanced the production of IFN-gamma, IL-1beta, and TNF-alpha. In vivo activity of adoptively transferred CD4 T cells required matching of HLA-DRB1 alleles and also the presence of T cell/B cell follicles. HLA-DRB1-matched synovial tissues that were infiltrated by T cells, macrophages, and dendritic cells, but that lacked B cells, did not support the activation of adoptively transferred CD4 T cell clones, raising the possibility that B cells provided a critical function in T cell activation or harbored the relevant Ag. Dependence of T cell activation on B cells was confirmed in B cell depletion studies. Treatment of chimeric mice with anti-CD20 mAb inhibited the production of IFN-gamma and IL-1beta, indicating that APCs other than B cells could not substitute in maintaining T cell activation. The central role of B cells in synovial inflammation identifies them as excellent targets for immunosuppressive therapy.

Serum cytokines in different histological variants of rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by an invasive and tissue destructive infiltrate of lymphocytes, macrophages, and synoviocytes formed in the joints. Its etiopathogenesis and the role of the particular morphological components of synovitis remain unclear. There is evidence that its histological heterogeneity is correlated with synovium cytokine transcription. We investigated whether the serum cytokine profile is associated with the morphological appearance of the disease. METHODS: Tissue and serum samples were collected from 25 patients with clinically active RA and 25 with osteoarthritis (OA) as a control group. After histological analysis RA synovial biopsies were divided into 2 distinct types; 16 samples were characterized by diffuse lymphocyte infiltrates with no additional microanatomical organization. Lymphocytic aggregates with germinal center-like structures were found in 9 specimens. Serum concentrations of interferon-gamma (IFN-gamma), interleukin 12 (IL-12, p70 heterodimer), tumor necrosis factor-alpha (TNF-alpha), and IL-15 were measured by ELISA. RESULTS: Low concentrations of IFN-gamma (p < 0.01) and IL-12 (NS) were found in RA patients' serum compared with OA controls. RA patients with follicular synovitis had lower serum concentration of IFN-gamma (p < 0.05) and IL-12 (p < 0.05) than patients with diffuse infiltrates. High concentration of TNF-alpha and IL-15 characterized RA patient serum in comparison with controls (respectively, p < 0.001 and p < 0.01). In the serum of RA patients with follicular synovitis TNF-alpha was a dominant cytokine (p < 0.01) compared to patients with diffuse disease. At TNF-alpha level > or = 44 pg/ml, 5 (56%) of 9 patients with follicular RA had such elevated values vs one of 16 diffuse patients (< 10%; p < 0.02). Only serum concentrations of TNF-alpha could effectively differentiate between patients with OA and subgroups of RA. Analysis of clinical data suggested that activity of rheumatoid disease in patients with follicular synovitis was more severe than in those with diffuse infiltrates. CONCLUSION: The association between distinct histological appearance of rheumatoid synovitis and serum cytokine profile and diverse clinical activity of disease seems to confirm its heterogeneity.

[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.

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.