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.

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.