The effect of interleukin-10 and of interleukin-12 on the in vitro production of anti-double-stranded DNA antibodies from patients with systemic lupus erythematosus

Abstract

SUMMARYIL-10 and IL-12 are cytokines which are important in regulating immune responses. Plasma levels of IL-10 and autoantibodies against double-stranded DNA (dsDNA) often mirror disease activity in patients with SLE. IL-12 secretion from SLE patients' blood mononuclear cells also correlates with disease activity, but has an inverse relationship. The aim of this study was to measure the effect of IL-10 and of IL-12 on the production of IgG autoantibodies from patients with SLE, both cross-sectionally and longitudinally. Peripheral blood mononuclear cells (PBMC) were cultured with IL-10 (at 20 ng/ml or 2 ng/ml) or IL-12 (at 2 ng/ml or 0´2 ng/ml) or without cytokine and the supernatanants tested for the production of doublestranded DNA antibodies (dsDNA abs), single-stranded DNA antibodies (ssDNA abs) and total IgG antibodies (IgG abs) by ELISA. The BILAG disease activity index was recorded at each patient visit (a global score of six or more is regarded as active disease). In general, treatment with IL-10 caused PBMCs from patients with inactive disease to increase their antissDNA and dsDNA ab production (by upto 354% and 186%, respectively) while patients with active disease decreased their antibody production (by upto 91% and 97%, respectively). Overall there was a correlation between disease activity and change in antissDNA and dsDNA ab production (r 2 0´51; P 0´03 and r 2 0´48; P 0´042, respectively). Treatment with IL-12 at 0´2 ng/ml inhibited antissDNA and dsDNA antibody production, having the greatest effect on patients with active disease (decreasing antissDNA and dsDNA antibody production by upto 75% and 73%, respectively). This resulted in a significant correlation between disease activity and change in antissDNA antibody production (r 2 0´76; P 0´03), but significance was not reached with antidsDNA antibody production (P 0´06). Together these data suggest that the effect of these cytokines on antibody production by SLE PBMCs involves several factors; one of which is disease activity.

Exhaled cytokines in systemic lupus erythematosus with lung involvement

“…The effect of IL-6 is mainly proinflammatory: the activation of IL-10 have been found to positively correlate with anti-ds DNA antibody titers and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and negatively with complement C3 levels. 19,20 However, in the present study, the IL-10 level in the EBC was found to correlate negatively with the activity of SLE, and it showed a similar tendency in the BALF. This finding could confirm that of Capper et al 18 regarding the coexistence of groups of SLE patients with different patterns of cytokine activity.…”

Mechanism and Regulatory Function of CpG Signaling via Scavenger Receptor B1 in Primary B Cells

“…In our studies, we have shown that dual engagement of SR-B1 and TLR9 by CpG negatively regulates the production of pro-inflammatory mediators such as IL-6 and IL-10. Although the role of these cytokines in promoting autoimmune disease is complex and not fully resolved, IL-6 and IL-10 are biomarkers of systemic lupus erythematosis (44) and have been implicated in its pathogenesis (45)(46)(47)(48)(49). IL-6 regulates B cell differentiation and Ig production, but this action seems more critical to isotype switching and not IgM production (50).…”

Aberrant Production of IL-12 by Macrophages from Several Autoimmune-Prone Mouse Strains Is Characterized by Intrinsic and Unique Patterns of NF-κB Expression and Binding to the IL-12 p40 Promoter

“…The potential for overexpression of IL-12 may predispose diabetes-prone mice toward a Th1-mediated pathway of organ-specific autoimmunity, while reduced IL-12 in lupus-prone mice would be expected to promote B cell-mediated systemic autoimmunity. Recent reports that IL-12 inhibits B cell function in a more proximal fashion (12,13) suggest additional mechanisms by which the deficiencies in IL-12 production in NZB/W and MRL/ϩ mice may contribute to B cell hyperactivity and autoantibody production. Recently, NF-B defects (specifically, reduced levels of p65) have been reported in T cells from lupus patients (21).…”

“…IL-12 plays a critical role in the selection and maintenance of the Th1 subset (1), which, in turn, is required for eliciting organspecific autoimmunity (11). Moreover, IL-12 has been shown to inhibit B cell function (12,13), suggesting that the reduced production of this cytokine in the MRL/ϩ and NZB/W strains could contribute to lupus as well. In the current study we have addressed the possible mechanisms underlying IL-12 dysregulation.…”