Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2008, vol. 17, nr 4, July-August, p. 415–421

Publication type: original article

Language: English

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

Aktywność iNOS w leukocytach krwi obwodowej u chorych na reumatoidalne zapalenie stawów i wczesne zapalenie stawów

Beata Nowak1,, Magdalena Sokalska−Jurkiewicz1,, Marta Madej1,, Ewa Zaczyńska2,, Anna Czarny2,, Jacek Szechiński1,

1 Department of Rheumatology and Internal Diseases Silesian Piasts University of Medicine in Wrocław, Poland

2 Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland

Abstract

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.

Streszczenie

Wprowadzenie. Tlenek azotu (NO) jest małą, bardzo aktywną chemicznie cząsteczką, która jest zaangażowana w wiele procesów fizjologicznych, m.in. odgrywa istotną rolę w regulacji procesów immunologicznych. Autorzy uprzednio opisywali podwyższone stężenie metabolitów NO w surowicy chorych na reumatoidalne zapalenie stawów i chorobę zwyrodnieniową stawów.
Cel pracy. Ocena aktywności iNOS w leukocytach krwi obwodowej pobranej od chorych na r.z.s. i w.z.s. Materiały i metody. Do badania włączono 35 chorych z ustalonym rozpoznaniem r.z.s., 31 chorych na w.z.s. i 30 zdrowych ochotników, jako grupę kontrolną. Ekspresję iNOS w leukocytach określano metodą immunocytochemiczną.
Wyniki. Średnia wieku chorych na r.z.s. wynosiła 57,7 lat, a chorych na w.z.s. 44,1 lat. Wysoką aktywność choroby definiowaną jako DAS28 > 5,1 stwierdzono u 18 chorych na r.z.s. (średnia wartość DAS28 w tej grupie wynosiła 5,0) i u 18 chorych na w.z.s. (średnia wartość DAS28 w tej grupie wynosiła 5,2). Średni czas trwania choroby wynosił w grupie chorych na r.z.s. 13,0 lat, a w grupie chorych na w.z.s. 6,5 miesiąca. Ekspresja iNOS w grupie chorych na r.z.s., w.z.s. i w grupie kontrolnej wynosiła odpowiednio 25,4% ± 15,2%, 18,7% ± 12,3% i 13,8% ± 15,1%, Wykazano istotną statystycznie różnicę między poszczególnymi grupami (p < 0,05). Wśród chorych na w.z.s. aktywność iNOS była istotnie wyższa u chorych palących papierosy (22,9% vs. 14,4%). Nie obserwowano analogicznej zależności w grupie chorych na r.z.s. W grupie chorych na r.z.s. stwierdzono istotną statystycznie korelację między ekspresją iNOS a stężeniem CRP, liczbą bolesnych i obrzękniętych stawów oraz DAS28. W grupie chorych na w.z.s. nie stwierdzono korelacji między ekspresją iNOS a wskaźnikami aktywności choroby.
Wnioski. Różnica aktywności iNOS w grupach chorych na r.z.s. i w.z.s. nie wynika z różnic w aktywności choroby, gdyż DAS28, OB i CRP są zbliżone w badanych grupach. Potrzebne są dalsze badania, które pozwolą na wyjaśnienie mechanizmów odpowiedzialnych za obserwowaną różnicę. Zwiększona aktywność iNOS u palaczy z w.z.s. wymaga także dalszych badań.

Key words

inducible nitric oxide synthase (iNOS), rheumatoid arthritis (RA), early arthritis (EA)

Słowa kluczowe

indukowana syntaza tlenku azotu (iNOS), reumatoidalne zapalenie stawów (r.z.s.), wczesne zapalenie stawów (w.z.s.)

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