Involvement of cytokines in the pathogenesis of systemic lupus erythematosus.

Abstract

Systemic lupus erythematosus (SLE) is characterized by overt polyclonal B-cell activation and autoantibody (Ab) production. By contrast, cellular immune responses against allo- or recall antigens are significantly impaired. Many evidences indicate that IL-10 overproduction plays a pivotal role in the disease and the contribution of the IL-10/IL-12 imbalance to the pathophysiology of SLE will be extensively discussed. The authors will further summarize the available data about the involvement of IFN-γ, TNF-α, TGF-β and TALL-1. Other cytokines (IL-1, IL-2, IL-4, IL-6, IL-16, IL-17 and IL-18) will be briefly discussed. Numerous abnormalities of the cytokine network have been described in patients suffering from systemic lupus erythematosus as well as in murine lupus models. Some of them were shown to play a pivotal physiopathological role in certain T-cell, B-cell or antigen-presenting cell (APC) dysfunctions characteristic of the disease, while others are more likely to be innocent bystanders. It should be stressed, moreover, that not all the data discussed herein fit into a single picture. The heterogeneity of human SLE, the influence of disease activity and therapy on cytokine production and function, the relative shortage of human lupus peripheral blood-derived mononuclear cells (PBMC), together with the lack of a perfectly-matched animal model, further sophisticate the issue. For these very reasons, this review will focus on the cytokines that the authors wrongly or rightly consider as the major players in the game, namely IL-10, IL-12, TNF-α, IFN-γ and the recently described TALL-1/BLys/BAFF. Before doing so, we felt worthwhile to briefly glance through the major immune abnormalities observed in SLE.