Systemic lupus erythematosus monocytes are less responsive to interleukin‐10 in the presence of immune complexes
Open Access
- 15 October 2010
- journal article
- systemic lupus-erythematosus
- Published by Wiley in Arthritis & Rheumatism
- Vol. 63 (1), 212-218
- https://doi.org/10.1002/art.30083
Abstract
Objective Systemic lupus erythematosus (SLE) is a systemic inflammatory disease characterized by autoantibody production and immune complex deposition. The level of interleukin‐10 (IL‐10), predominantly an antiinflammatory cytokine, is paradoxically elevated in patients with SLE. The aim of this study was to examine the hypothesis that the antiinflammatory function of IL‐10 is impaired in monocytes from patients with SLE with long‐term exposure to immune complexes. Methods CD14+ monocytes were isolated from healthy donors and patients with SLE. Cultured CD14+ cells were treated with heat‐aggregated human IgG (325 μg/ml) in the presence or absence of IL‐10 (20 ng/ml). To study gene expression, RNA was extracted 3 hours after treatment. To study cytokine production, supernatants were harvested after 8 hours. To study IL‐10 signaling, cell lysates were obtained from CD14+ cells treated with human IgG (325 μg/ml) for 1 hour followed by IL‐10 (20 ng/ml) treatment for 10 minutes. Western blot analysis was used to assess STAT‐3 phosphorylation. All experiments were performed in pairs. Results When stimulated with human IgG, SLE monocytes produced more tumor necrosis factor α (TNFα) and IL‐6 than did control cells. The suppressive effect of IL‐10 on human IgG–induced TNFα and IL‐6 production was lower in SLE monocytes compared with control monocytes, although IL‐10 receptor expression was similar in SLE and control monocytes. Human IgG suppressed IL‐10 receptor expression and altered IL‐10 signaling in control monocytes. Like SLE monocytes, interferon‐α (IFNα)–primed control monocytes stimulated with human IgG were also less responsive to IL‐10. Conclusion Human IgG and IFNα modulate IL‐10 function. In SLE monocytes, which are considered to be IFNα primed and persistently exposed to immune complexes, responses to IL‐10 are abnormal, limiting the antiinflammatory effect of this cytokine.Keywords
This publication has 26 references indexed in Scilit:
- Interleukin-6 release from peripheral mononuclear cells is associated to disease activity and treatment response in patients with lupus nephritis.Lupus, 2009
- The role of tumor necrosis factor-alpha in systemic lupus erythematosusArthritis Research & Therapy, 2008
- Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid ArthritisThe Journal of Experimental Medicine, 2003
- Modulating macrophage function with IgG immune complexesInnate Immunity, 2002
- Modulating macrophage function with IgG immune complexesInnate Immunity, 2002
- Interleukin-10 and the Interleukin-10 ReceptorAnnual Review of Immunology, 2001
- Increased number of interleukin-10-producing cells in systemic lupus erythematosus patients and their first-degree relatives and spouses in Icelandic multicase familiesArthritis & Rheumatism, 1999
- Dysregulation of interleukin‐10 production in relatives of patients with systemic lupus erythematosusArthritis & Rheumatism, 1997
- Immune complex‐induced interleukin‐6, interleukin‐10 and prostaglandin secretion by human monocytes: a network of pro‐ and anti‐inflammatory cytokines dependent on the antigen: antibody ratioEuropean Journal of Immunology, 1996
- The 1982 revised criteria for the classification of systemic lupus erythematosusArthritis & Rheumatism, 1982