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Vidosava B. Đorđević, Ivana Stojanović, Slavica Kundalić, Tatjana Ristić, Radmila Pavlović, Vladan Ćosić and Tatjana Cvetković

Summary

Nitric oxide (NO) is produced by many cells in the body; however, its production by vascular endothelium is particularly important in the regulation of blood flow. Vascular actions of NO include the following: direct vasodilation, indirect vasodilation by inhibiting the vasoconstrictor influences, anti-thrombotic, anti-inflammatory and anti-proliferative effects. Due to its importance in vascular function, abnormal production of NO, occurring in different diseases can adversely affect blood flow and other vascular functions. It has been suggested that alterations in NO generation are a critical cause of injury in the ischemic heart. A biologic link between the endothelial damage and atherosclerotic coronary arterial disease has been presumably related to de - creased arterial bioavailability of NO through the increased leucocyte and platelet adhesions, vasoconstriction and smooth muscle cell proliferation. However, the precise me - chanism of the impaired NO generation is not known, and there is a considerable controversy regarding whether myo - cardial ischemia results in increased or decreased NO for - mation. Asymmetric dimethylarginine (ADMA) is a natural, com petitive inhibitor, and one of the primary factors controlling the nitric oxide production. ADMA was found to be elevated and closely correlated with the impaired vasodilator function in conditions associated with the endothelial dysfunction, such as hypercholesterolemia, hypertension, insulin resistance and type 2 diabetes, and renal failure. But ADMA also seems to be involved in myocardial ischemia, since its plasma levels predict future coronary events in patients with the elevated cardiovascular risk. It has been recently reported that the elevated plasma ADMA concentrations in the acute coronary events are an independent cardiovascular risk factor.

Open access

Lilika Zvezdanović, Vidosava Đorđević, Vladan Ćosić, Tatjana Cvetković, Slavica Kundalić and Aleksandra Stanković

The Investigation of Cytokines and Oxidative Stress in Patients with Systemic Lupus Erythematosus

Numerous factors can influence the onset of SLE and development of some clinical disease manifestations with various organ involvements and occurrence of characteristic symptoms and disease signs. This paper studies the balance between proinflammatory and antiinflammatory cytokines, investigates the presence of oxidative stress measuring certain prooxidative factors and determines the activation of antioxidative protection pathways aiming to establish possible correlations between the studied parameters. ELISA, enzymatic spectrophotometry and colorimetric methods were used to determine the above-mentioned parameters. The results obtained indicate that disturbed pro/antioxidative status is associated with the change of antioxidative factors, with the fall od SOD activity and increase of GPx and CAT activity in the erythrocytes of all studied groups of patients. At the same time, the cytokine production was altered, not only compared to the healthy control samples, but also in various clinical disease manifestations. Altered relationships of pro and antiinflammatory cytokines and the consequential disorders of other studied systems provide us with useful strategic targets for diagnostic monitoring and possible therapeutic interventions in SLE patients.

Open access

Vidosava Đorđević, Lilika Zvezdanović, Vladan Ćosić, Predrag Vlahović, Slavica Kundalić, Tatjana Jevtović-Stoimenov, Bojana Stamenković and Dragoslav Mitrović

Serum Levels and in Vitro Production of Th1- and Th2-Type Cytokines by Peripheral Blood Mononuclear Cells in Patients Suffering from Systemic Lupus Erythematosus

Th1-type and Th2-type cytokine profiles and adhesion molecules in the serum of patients suffering from systemic lupus erythematosus and the cytokine production by peripheral blood mononuclear cells (PBMC) were studied. Tumor necrosis factor-alpha (TNF-α), interferongamma (IFN-γ), interleukin-1β (IL-1β), IL-4, IL-10, IL-13, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured using ELISA technique in the sera of 16 systemic lupus erythematosus patients without vasculitis (SLE), 30 SLE patients with vasculitis (LV), and in 18 healthy controls. The cytokines were also measured in the culture media of unstimulated, concana valin-A (Con-A) and phorbol-12-myristate-13-acetate (PMA) stimulated PBMC. TNF-α serum levels were significantly elevated in both SLE and LV patients and those of IL-1β in SLE patients. TNF-α was also significantly increased in SLE compared to LV patients. Serum levels of all three Th-2 cytokines were significantly elevated in both SLE and LV patients compared to healthy controls. Serum IFN-γ and Th2 cytokine levels were significantly increased in patients with more active disease. Both ICAM-1 and VCAM-1 were significantly increased in SLE patients and only VCAM-1 in LV patients. ICAM-1 showed a significant correlation with IL-1β, IFN-γ, IL-4 and IL-10 in both patient groups. In the SLE group VCAM-1 correlated significantly only with ICAM-1, but in the LV group only with IL-1β and IFN-γ. Compared to healthy controls, basal TNF-α and IL-4 production by unstimulated PBMC derived from SLE patients were significantly increased. Con-A-stimulated PBMC of both SLE groups produced significantly more IFN-γ, IL-4 and IL-13 than Con-A-stimulated control cells. Con-A-stimulated cells derived from LV patients produced much more INF-γ than cells from SLE patients. PMA strongly stimulated INFγ, TNFα and IL-13 production by cells derived from both SLE groups but had no effect on IL-4 production. In addition, it had little if any effect on the production of INFγ and IL-13 by PBMC derived from healthy donors. These findings suggest that the altered pattern of cytokine production by PBMC may play an important role in the SLE pathophysiology, accounting for differences in the clinical expression of the disease. The differences in adhesion molecules production and their correlation with cytokines suggest ICAM-1 and VCAM-1 as useful markers in SLE patients stratification.