iNOS Expression in Peripheral Blood Leukocytes of Patients With Early Arthritis and Established Rheumatoid Arthritis

Background. Nitric oxide (NO) is a small, very reactive molecule involved in many physiological processes; including immune response. The present authors previously reported increased levels of NO metabolites in the serum of patients with rheumatoid arthritis (RA) and osteoarthritis. Objectives. The aim was to evaluate the activity of iNOS in peripheral blood leukocytes (PBLs) in patients with early arthritis (EA) and established RA and to compare it with parameters of disease activity used in clinical practice. Material and Methods. Thirty-five patients who met the ACR criteria for RA, 31 patients with EA, and 30 healthy controls were enrolled in the study. The activity of iNOS was measured by an immunocytochemical method in PBLs separated by density gradient. Results. The mean age of RA patients was 55.7 years. High disease activity (defined as DAS28 > 5.1) was detected in 18 patients and mean DAS28 was 5.0. Mean disease duration was 13.0 years. The mean age of EA patients was 44.1 years. High disease activity was detected in 18 patients and mean DAS28 was 5.2. Mean disease duration was 6.5 months. There was a statistically significant (p < 0.05) difference between RA and EA patients and healthy subjects in iNOS expression (25.4 +/- 15.2%, 18.7 +/- 12.3%, and 13.8 +/- 15.1%, respectively). In EA the mean iNOS expression was higher in patients with cigarette abuse than in nonsmokers (22.9% vs. 14.4%), whereas no such a difference was observed in established RA. In established RA, iNOS expression Correlated with CRP level, the number of tender and swollen joints, and DAS28. In EA, no correlation between iNOS expression and the analyzed parameters of disease activity was found. Conclusion. As the difference between iNOS expression in PBLs in patients with RA and with EA cannot be attributed to differences in disease activity (DAS28 score, ESR, and CRP level are similar in both groups), further observation is needed to determine whether higher iNOS expression in some patients with early arthritis can predict future RA development. The higher iNOS expression in smokers with EA needs further study aimed at determining if smoking induces iNOS activity and thereby promotes RA development (Adv Clin Exp. Med 2008, 17, 4, 415-421).