Systemic lupus erythematosus monocytes are less responsive to interleukin-10 in the presence of immune complexes.
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.


CONCLUSIONS
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.
Hospital for Special Surgery and Weill Cornell Medical College, New York, New York 10021, USA.
Weijia
W
Yuan
Stephen J
SJ
DiMartino
Patricia B
PB
Redecha
Lionel B
LB
Ivashkiv
Jane E
JE
Salmon
D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000936:Antigen-Antibody Complex; D016207:Cytokines; D007074:Immunoglobulin G; D012333:RNA, Messenger; D016753:Interleukin-10