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

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

doi:10.2478/v10011-010-0005-z

Abstract

Serum Levels and in Vitro Production of Th1- and Th2-Type Cytokines by Peripheral Blood Mononuclear Cells in Patients Suffering from Systemic Lupus ErythematosusTh1-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.

Highlights

systemic lupus erythematosus patients without vasculitis (SLE) is a chronic inflammatory disease of unknown etiology which may involve multiple tissues and organs, leading to/or resulting from a disturbance in immune regulation characterized by excessive production of autoantibodies directed against various cell and tissue antigens [1]
A DNA fragment is suspected to interact with adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressed on vascular endothelial cells (VEC) and activate the production of proinflammatory cytokines (IL-6, IL-8, Tumor necrosis factor-alpha (TNF-a), and IFN-g) [7]
ICAM-1 is an initial marker of inflammatory response induced by IL-1, TNF-a, or, IFN-g, whilst VCAM-1 production is regulated by TNF-a, IL-1, and IL-4

Summary

Introduction

SLE is a chronic inflammatory disease of unknown etiology which may involve multiple tissues and organs, leading to/or resulting from a disturbance in immune regulation characterized by excessive production of autoantibodies directed against various cell and tissue antigens [1]. This immune disturbance seems to result from the interplay of genetic, environmental and hormonal factors [1, 2]. Vasculitis is characterized by perivascular infiltration with proinflammatory cells and by damage to blood vessel walls It may be the primary manifestation of a disease or secondary component of another primary disease, including SLE [5]. ICAM-1 is an initial marker of inflammatory response induced by IL-1, TNF-a, or, IFN-g, whilst VCAM-1 production is regulated by TNF-a, IL-1, and IL-4

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Conclusion