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Ann Rheum Dis. 2003 Jan; 62(1): 37–42.
PMCID: PMC1754302

Immune complexes from SLE sera induce IL10 production from normal peripheral blood mononuclear cells by an FcγRII dependent mechanism: implications for a possible vicious cycle maintaining B cell hyperactivity in SLE


Background: Raised interleukin (IL)6 and IL10 levels are thought to contribute to the pathogenesis of systemic lupus erythematosus (SLE) by enhancing autoantibody production and immune complex (IC) formation. These immune complexes can then stimulate cellular reactions through Fc and complement receptors.

Objective: To investigate whether circulating SLE ICs stimulate type 2 cytokine production.

Methods: Twenty serum samples from patients with active SLE were compared with sera from 18 healthy controls. Sera and polyethylene glycol (PEG) precipitates from sera were added to peripheral blood mononuclear cell (PBMC) cultures, and the production of IL10 and IL6 was investigated by enzyme linked immunospot assay (ELISPOT) and enzyme linked immunosorbent assay (ELISA). Fc gamma receptor (FcγR) antibodies were used in blocking experiments, and flow cytometry was used to assess the correlation between monocyte FcγR expression and IC-induced cytokine production.

Results: Ten per cent dilutions of the SLE sera induced a significantly increased number of IL10-producing cells in comparison with control sera (median, 11.75 v 1.25 spot forming cells/50 000 PBMC; p<0.0001). PEG precipitates from SLE sera also induced significantly increased levels of IL10 (p=0.016) and IL6 (p=0.042) in comparison with control PEG precipitates. IL10 production induced by SLE PEG precipitates or by artificial ICs could be blocked by anti-FcγRII antibodies, and the FcγRII expression on CD14+ monocytes correlated with the IC-induced production of IL10 and IL6.

Conclusions: SLE sera stimulate IL10 and IL6 production from PBMC, and this effect is at least partly explained by precipitable ICs acting through FcγRII. This effect provides a possible mechanism for the enhanced production of IL10 in SLE, whereby B cell activation, antibody production, IC stimulated monocytes/macrophages, and type 2 cytokines create a vicious cycle that may help to maintain B cell hyperactivity in SLE.

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Selected References

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Figures and Tables

Figure 1
Heat aggregated IgG induces production of IL10 and IL6 in cultures of human PBMC by increasing the number of cells producing IL10, but not IL6. Human monomeric IgG was heat aggregated and diluted to various concentrations in PBS, and then added to PBMC ...
Figure 2
SLE sera stimulate an increase in the number of IL10 SFC. Twenty serum samples from patients with SLE and 18 sera from healthy controls (10% of final volume) were added to 100 µl PBMC suspensions from a healthy donor (5x105 cells/ml) in duplicate. ...
Figure 3
High molecular weight PEG precipitates from SLE sera induce IL10 and IL6 production in human PBMC cultures. Serum samples from 16 patients with SLE and 17 healthy controls were subjected to PEG precipitation, and the precipitates were diluted to the ...
Figure 4
Effects of blockade of FcγRII and FcγRIII on IC-induced cytokine production. Cell cultures were incubated with 1.5 µg/ml of blocking Fab (FcγRII) or F(ab‘)2 (FcγRIII) fragments for 30 minutes before addition ...

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