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In the present study, in order to get a better insight into the mechanism of action of cyclophosphamide (CY) in rheumatoid arthritis (RA), we monitored the changes in lymphocytes' expression of leukocyte function associated antigen 1 (LFA-1). A group of 28 patients with refractory severe RA were treated with CY and methylprednisolone (MO) intravenously. Using flow cytometry we evaluated the changes in LFA-1 molecule expression on peripheral lymphocytes. In the analyzed group of patients the proportion of LFA-1 "dim" cells was reduced. After the treatment the ratio was partly normalized. Twelve months after cessation of the therapy high proportion of LFA-1 "dim" was observed only among CY/MP treated patients. The changes were related to clinical improvement. Based on the obtained data, it seems, that the treatment affecting the expression of LFA-1 may slow down lymphocyte migration and by that limit chronic inflammation within the synovium.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the effect of interleukin 10 (IL-10) on acute phase response, we determined serum levels of IL-10, interleukin 6 (IL-6), C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), alpha-1-anti-chymotrypsin (ACT) in 34 rheumatoid arthritis (RA) patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). CRP, AGP and ACT levels were measured using rocket immunoelectrophoresis. The results showed that IL-10 serum level was increased in RA patients as compared to controls (60.0 +/- 17.5 pg/ml vs. 7.2 +/- 1.9 pg/ml). IL-6 level was significantly elevated (87.3 +/- 32.7 pg/ml vs. 45 +/- 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (34 +/- 19 mg/1 vs. 3 +/- 2 mg/1, p < 0.05). AGP and ACT serum levels were increased in RA patients, but we did not find these changes to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = -0.73, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.74, p < 0.05) and ACT (r = 0.45, p < 0.05) was established. Moreover, a negative correlation between IL-10 and serum level of CRP (r = -0.76, p < 0.05), AGP (r = -0.60, p < 0.05) and ACT (r = -0.37, p < 0.05) was also shown. According to the data thus far obtained it seems that IL-10 decreases IL-6 production, and by that indirectly affects acute phase response, decreasing CRP, AGP and ACT synthesis.

Twenty three rheumatoid arthritis (RA) patients treated with cyclophosphamide (CTX) were observed for 6 months. Eight patients received CTX in a single intravenous dose (group I) and 15 orally in a single daily dose (group II). The surface antigens of lymphocytes, isolated from peripheral blood, were determined using immunofluorescence method. The clinical improvement was observed both in group I and in group II of patients. However, in patients receiving CTX intravenously amelioration of the disease appeared quicker. The percentage of CD3+ and CD8+ T cells remained unchanged. In group I we observed decrease in the number of CD4+ T cells (60.1 +/- 11.5% and 43.8 +/- 12.5%, before and after treatment respectively, p < 0.01), in group II this level remained unchanged. In both groups the percentage of CD19+ B cells decreased (14.7 +/- 9.2% and 8.0 +/- 6.1%, before and after treatment respectively in group I, p < 0.01; 17.4 +/- 12.3% and 11.0 +/- 7.1%, before and after treatment respectively in group II, p < 0.01). Moreover, the percentage of activated T cells (CD25+ cells and HLA-DR+ cells) was reduced in both groups.

Seventy nine patients with rheumatoid arthritis (RA) were monitored for 12 months. Forty eight individuals were treated weekly with a low dose of methotrexate (MTX), and 31 received nonsteroid antiinflammatory drugs (NSAID) only. The mean total dose of MTX was 413 mg with a range from 250 to 735 mg. The phenotype of lymphocytes was analyzed using double immunofluorescence and a panel of monoclonal antibodies. The clinical status of 33 MTX-treated patients improved, in 9 neither clinical nor laboratory improvement was noticed. Six patients were withdrawn from the study because of adverse reactions. We observed no changes in the percentage of CD3, CD4, CD8 and CD25 positive lymphocytes in both MTX and NSAID-treated groups. However, the percentage of CD19 positive cells significantly decreased during 12 month observation (15.1 +/- 6.5% v.s. 10.2 +/- 5.0, p < 0.01) in MTX-treated subjects. Moreover, this percentage increased (9.4 +/- 6.7% v.s. 17.1 +/- 1.1%, p < 0.01) in NSAID-treated patients.