Cytokine disturbances in systemic lupus erythematosus

Abstract

The pathogenesis of systemic lupus erythematosus (SLE) is complex, and the resulting disease manifestations are heterogeneous. Cytokine dysregulation is pervasive, and their protein and gene expression profiles may serve as markers of disease activity and severity. Importantly, biologic agents that target specific cytokines may represent novel therapies for SLE. Four cytokines (IL-6, TNFα, IFNα, and BLyS) are being evaluated as therapeutic targets in SLE. The present review will examine the roles of each of these cytokines in murine and human SLE, and will summarize results from clinical trials of agents that target these cytokines.

An ENU Mutagenesis-Derived Mouse Model with a Dominant Jak1 Mutation Resembling Phenotypes of Systemic Autoimmune Disease

“…34 Increased levels of IL-6 have also been observed in serum of patients with SLE, especially during disease activity. 53,54 We observed that Jak1 S645Pþ/À mice showed a strong increase of IL-6 and elevated phosphorylation of IL-6 receptor gp130 and Stat-3 in the dermis. These new findings emphasize that Jak1 S645Pþ/À mice might model human SLE.…”

Hypergammaglobulinemia is a marker of extraintestinal manifestations in pediatric inflammatory bowel disease

“…Polyclonal B-cell activation by inflammatory cytokines, including B-cell activating factor and interleukin 6 (IL-6), plays an important role in lupus and other autoimmune conditions (12,13). IL-6 overexpression is a common feature of many autoimmune disorders, including IBD and autoimmune joint diseases (14,15); thus, it is probably a key determinant in the etiology of elevated IgG levels in IBD and EIM patients.…”

Modulating the survival and maturation system of B lymphocytes: Current and future new therapeutic strategies in systemic lupus erythematosus

“…Some phenotypic alterations have been correlated with periods of SLE activity and the presence of various soluble factors such as tumor necrosis factor (TNF) and B-cell activation factor (BAFF). [13][14][15] These changes raise several questions: Are they due to an intrinsic B cell abnormality, mistakenly programmed from its origin in the bone marrow? Can they be due to changes in the processes of proliferation, maturation, differentiation, survival and homeostatic control of B lymphocytes?…”