Interleukin-10 (IL-10) secretion in systemic lupus erythematosus and rheumatoid arthritis: IL-10-dependent CD4+CD45RO+ T cell-B cell antibody synthesis

Abstract

Interleukin-10 (IL-10) is a major immunoregulatory cytokine and has a multitude of immunomodulatory effects in the immune system. In this study, we have examined the secretion and in vitro function of IL-10 in B cell hyperactivity in antibody production in two common autoimmune diseases, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). IL-10 was detectable in serum of all active SLE and serum and synovial fluid samples of all RA patients but in none of the normal controls. B cells and CD4+CD45RO+ "memory" T cells secreted highly enhanced levels of IL-10 in SLE and RA versus normals. Increased IgM and IgG production by B cells-CD4+CD45RO+ T cells in SLE and RA was IL-10 dependent, since neutralization of IL-10 cytokine by anti-IL-10 antibody drastically reduced Ig synthesis in these coculture experiments. B cell hyperactivity in autoantibody production in SLE and RA may be a function of IL-10-dependent CD4+CD45RO+ Th2 cell activation. Therefore, IL-10 may play an important role in highly disturbed immune system and B cell-T cell function in these immune disorders.

Cytokines and systemic lupus erythematosus

“…This increase is mainly attributable to an increase in IL10 production by monocytes, a subset of B cells and possibly CD4+CD45 RO+ memory T cells 960 61 Serum titres of IL10 are positively correlated with anti-ds DNA antibody titres and the SLEDAI score and negatively correlated with complement C3 levels 6263 IL10 increases IgG production by PBMCs from patients with SLE 64.…”

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

“…Serum samples from 16 patients with SLE and 17 healthy controls were subjected to PEG precipitation, and the precipitates were diluted to the original serum volume in PBS. Ten per cent (final concentration) of each precipitate was added to a 250 µl suspension of PBMC (1×106 cells/ml) from the healthy subject investigated in fig 2. After incubation for 20 hours, supernatant levels of (A) IL10 and (B) IL6 were assessed by ELISA.…”

Induction of tumour necrosis factor receptor-expressing macrophages by interleukin-10 and macrophage colony-stimulating factor in rheumatoid arthritis

“…High levels of IL-10, M-CSF, and TNF-α expression have all been detected in the inflamed joint of RA [14,23,28,29]. To confirm the interaction of these cytokines in macrophage differentiation at the site of inflammation, ST samples from five patients with RA were analysed by two-color immunofluorescence labeling using Abs against IL-10R1, M-CSFR, and TNF receptors, as well as anti-CD68 Ab.…”

“…Furthermore, most of the IL-10 effects on B-cell function are stimulatory. IL-10 has been implicated in the maturation of B cells into plasma cells in the presence of synovial fibroblasts from RA [40], the spontaneous IgM-RF production by B cells [41], and the Th2 cell-mediated B-cell Ig production [29]. These B-cell stimulatory effects of IL-10 could be important in the perpetuation of RA inflammation because an inflammatory role of B cells in the pathogenesis has recently been supported by clinical efficacy of B-cell depletion therapy with anti-CD20 Ab in patients with RA resistant to TNF-α inhibitors [42].…”