Stefan Mackiewicz

INTERLEUKIN-10 AND INTERLEUKIN-6 IN LUPUS ERYTHEMATOSUS AND RHEUMATOID ARTHRITIS, CORRELATIONS WITH ACUTE PHASE PROTEINS

SummaryWe sought to investigate the influence of interleukin-10 (IL10) and IL-6 on the acute phase proteins (APP) in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). IL-10, IL-6, Creative protein (CRP), alpha-1-acid glycoprotein (AGP), and alpha1 antichymotrypsin (ACT) serum levels were determined in one hundred-eight patients (71 with SLE, 37 with RA).Quantification of the serum IL-10 level showed increased levels in SLE and RA patients as compared to healthy controls. Serum IL-6 level was found to be elevated in SLE and RA patients. A correlation between IL-10 and IL-6 serum level was found only in SLE. CRP and AGP serum levels were increased in RA as compared to controls, whereas in SLE only AGP was found elevated. A statistically significant correlation between IL-6 serum level and CRP, AGP and ACT was found only in RA. No correlation between IL-10 and serum level of CRP, AGP and ACT was established.Since IL-10 has a potent immunosuppressive activity, we expected it to be negatively correlated with APP levels. Surprisingly, IL-10 did not correlate with APP either in SLE or RA patients. However, the elevation of IL-10 serum levels in SLE and RA and the correlation between IL-10 and IL-6 in SLE may suggest that IL-10 may play a central role in inflammatory connective tissue diseases.

Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: preliminary report.

In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 ± 18.1 pg/ml vs. 57.2 ± 11.9 pg/ml). IL-6 level was significantly elevated (91.6 ± 46.9 pg/ml vs. 45 ± 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 ± 19 mg/l vs. 3 ± 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = −0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established. On the other hand, a negative correlation between IL-10 and serum level of CRP (r = −0.76, p < 0.05), AGP (r = −0.64, p < 0.05) and ACT (r = −0.38, p < 0.05) was also observed. Moreover, these relationships were maintained when patients treated with MTX, IMG, or NSAID were analyzed independently. According to the data thus far obtained, it seems that IL-10 decreases IL-6 production, and thereby indirectly affects the acute phase response, decreasing CRP, AGP, and ACT concentration in RA patients.

Cardiac valvular disease in patients with systemic lupus erythematosus. Relationship with anticardiolipin antibodies

We performed two-dimensional and Doppler echocardiography in 52 patients with systemic lupus erythematosus and in 34 healthy controls. In 25 patients (48.1%) echocardiographic disturbances were found (25/52 vs 2/34, p<0.001). Valvular abnormalities were detected in 18 patients (34.6%) but in only two controls (18/52 vs 2/34, p<0.01). The mitral valve was involved in 12 patients (23.1%). The most frequent finding was mild (13.5%) and moderate (9.6%) regurgitation or valvular thickening (9.6%). The aortic valve was involved in six and the tricuspid valve in three patients (11.5% and 5.8%, respectively). Only one patient had echocardiographic non-infective verrucous vegetation affecting the tricuspid valve. We did not observe significant hemodynamic valve disease. Endocardial findings were related to disease duration (p<0.05) but not to disease activity. Twenty-eight SLE patients (53.8%) had increased anticardiolipin antibodies (aCL). Patients with aCL (particularly those with IgG class) were characterized by a high incidence of echocardiographic abnormalities (p<0.001), mainly valvular (mitral or aortic) regurgitation (p<0.05). We found a relationship between anticardiolipin antibodies and disease activity (p<0.05). In conclusion, we postulate a prominent role for anticardiolipin antibodies in the pathogenesis of heart valve disease in patients with SLE.

Comparison of microheterogeneity of alpha-1-acid-glycoprotein in serum and synovial fluid from rheumatoid arthritis patients

SummaryMicroheterogeneity of alpha-1-acid glycoprotein was studied using affinity immunoelectrophoresis with concanavalin A as a ligand in the samples of serum and synovial fluid obtained at the same time from 22 patients with rheumatoid arthritis. Individuals with intercurrent infection or other illnesses were excluded from the study. The results were expressed as reactivity coefficient (RC). Disease activity was evaluated by Mallya-Mace Activity Score, Lansbury Joint Index and laboratory tests. In most of the studied samples the glycosylation pattern was similar, composed of a nonreactive variant and 2 reactive (the first and the second) with Con A variants. In seven samples of synovial fluid an extra third peak representative of the strongly reactive one with Con A fraction was observed. It was the cause of the remarkable elevation of AGP-RC. Moreover, the level of IgM and IgA RF was higher in the synovial fluid derived from these patients — with the presence of the third peak in AFF-EP with Con A — than in those without the considered fraction.

Blood Serum Levels of Amino-Terminal Pro-C-Type Natriuretic Peptide in Patients with Systemic Sclerosis

The aim of this pilot study was to examine the association of serum levels of amino-terminal fragment of pro-C-type natriuretic peptide (NT-proCNP), as a substitute measure of serum C-type natriuretic peptide (CNP), with clinical and laboratory findings in patients with systemic sclerosis (SSc). Serum NT-proCNP, soluble (s)E-and sP-selectin levels were examined using specific enzyme-linked immunosorbent assay in 30 patients with SSc and 30 healthy controls. We found no statistically significant difference in serum levels of NT-proCNP neither between patients with SSc and healthy controls nor between those treated with immunosuppressive agents and untreated patients. Nevertheless, in the investigated SSc group, serum NT-proCNP levels correlated with the concentrations of C-reactive protein (CRP) and the duration of the disease. Both sP- and sE-selectin levels were elevated in SSc patients when compared to healthy subjects. Also they did not correlate with the concentrations of NT-proCNP. The results of the study indicate that serum NT-proCNP level is likely secondary to existing inflammation. However, the magnitude of CNP action in SSc and its possible role in the pathogenesis of the disease remains to be elucidated.

Do Changes in Clinical Improvement in Rheumatoid Arthritis Patients Treated with Immunosuppressive Drugs Reflect the Changes in acute Phase Proteins

We sought to investigate whether clinical improvement after immunosuppressive treatment reflects changes in acute phase response (APR) in rheumatoid arthritis (RA). Fifty-eight patients (pts) were treated with methotrexate (MTX), nineteen with intravenous cyclophosphamide (CTX), and fifteen with cyclosporin A (CSA). C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), alpha-1 antichymotrypsin (ACT), and alpha-1 antitrypsin (AT) serum levels were measured by nephelometry or rocket immunoelectrophoresis. Clinical improvement was observed in 67% MTX pts, 53% CTX pts, and 47% CSA pts. Baseline serum levels of CRP, AGP, ACT, and AT were significantly higher as compared to healthy controls. After MTX and CTX therapy CRP level significantly decreased. The decrease in serum level of ACT and AT in CTX treated patients was also observed. All analyzed acute phase proteins remained substantially elevated after CSA therapy despite a clear reduction in disease activity. We established a correlation between changes in disease activity and all acute phase proteins (APP) in MTX and CTX pts. From our study we can conclude that clinical improvement after immunosuppressive treatment correlated with quantitative changes in all APR markers in MTX and CTX treated pts, and none in CSA pts. Although measurement of APP remains the best marker for monitoring RA pts, not always they properly reflect changes in disease activity.

Does methotrexate affect serum level of IgA-alpha-1 antitrypsin complex in early rheumatoid arthritis?

SummaryWe followed the levels of serum IgA-alpha-1-antitrypsin complex (IgA-AT), C-reactive protein (CRP), alpha-1-acidglycoprotein (AGP), and alpha-1-antichymotrypsin (ACT) in twenty-seven early rheumatoid arthritis (RA) patients during the first three years of the disease duration. Fifteen patients were treated with methotrexate (MTX), twelve patients with NSAIDs only.The IgA-AT serum concentrations were significantly higher in RA patients as compared to the control group (0.72±0.39 U, vs. 0.27±0.15 U, p<0.01). It decreased in almost all individuals (23 cases) during the observation. This decrease occurred in both MTX treated and untreated patients; however, it was statistically significant (p<0.01) only in MTX treated patients.On average, the levels of ESR, CRP, AGP, and ACT were higher at the beginning of the disease as compared to healthy controls. After three years duration of the disease, a significant decrease in serum levels of all these markers of acute phase response was observed. At the onset of the disease, AGP and ACT reactivity coefficients were normal; after three years they dropped.We demonstrated an association between IgA-AT level and erythrocyte sedimentation rate. No relationships were shown between IgA-AT levels and APP serum concentrations and APP glycosylation patterns in RA patients treated with MTX. Since decrease in IgA-AT level does not correlate with decrease in APP, we can suppose that observed changes in IgA-AT concentration depend rather on direct action of MTX on the complex, than the changes in disease course. Besides gold salts, D-penicillamine, and sulphasalazine, methotrexate may also destroy covalent linkage between IgA and antitrypsin.