Relationship of oncogenes (sFas, Bcl-2) and cytokines (IL-10, alfa-TNF) with the activity of systemic lupus erythematosus

Abstract

Background: Different oncogenes (Fas and bcl-2) and diverse cytokines (IL-10 and alfa-TNF) may have an effect on the regulation of apoptosis. The majority of studies to date have evaluated only one or two of these elements independently and it is difficult to obtain a global view of apoptosis disregulation in the pathogenesis of systemic lupus erythematosus (SLE) and their role in disease activity. The aim of this study was to evaluate serum levels of sFas, bcl-2, IL-10 and alfa-TNF in human SLE patients and to analyze their relationship with disease activity and with regulation of the apoptotic process.

Patients and methods: Serum levels of sFas and cytokines IL-10 and alfa-TNF were studied by enzyme-linked immunoabsorbent assay. Bcl-2 antigen expression was analyzed in lysated lymphocytes from 51 SLE patients. The disease activity was analyzed according to the SLE disease activity index (SLEDAI).

Results: SLE patients had higher levels of sFas (p=0.0006) and alfa-TNF (p<0.0001) than the control group. No relationship was found between the levels of bcl-2 and IL-10 from SLE patients and the control group. However, there was a significant correlation between SLEDAI and bcl-2 (p<0.001) and IL-10 levels (p=0.004). In contrast, we found that sFas and alfa-TNF were not related with disease activity. A significant correlation of sFas with alfa-TNF serum levels (p=0.003, R= +0.41) and bcl-2 antigen expression (p=0.02, R=+0.32) was observed.

Conclusion: sFas and alfa-TNF serum levels are increased in SLE patients. sFas levels seems to be secondary to alfa-TNF action, which is enhanced in inflammatory conditions such as SLE. Bcl-2 antigen expression and IL-10 serum levels are related to the maintenance of SLE activity. These alterations may interfere with the apoptotic process, promoting lymphocyte hyperactivity secondary to increased cytokine levels, and causing the characteristic features of SLE.