Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus.

TLDR

Interleukin‑10 is produced at markedly elevated levels by B lymphocytes and monocytes in patients with systemic lupus erythematosus. The study examined whether this heightened IL‑10 production drives the abnormal immunoglobulin and autoantibody production seen in SLE. The authors compared IL‑10 with IL‑6 by stimulating peripheral blood mononuclear cells in vitro with recombinant cytokines and by administering anti‑IL‑6 and anti‑IL‑10 antibodies to SCID mice engrafted with SLE PBMCs. Recombinant IL‑10 strongly stimulated IgM, IgG, and IgA secretion, whereas anti‑IL‑10 antibodies markedly reduced autoantibody and total IgG production in vitro and in vivo, demonstrating that SLE B‑cell hyperactivity is largely IL‑10 dependent.

Abstract

Interleukin-10 (IL-10) is produced at a high level by B lymphocytes and monocytes of patients with systemic lupus erythematosus (SLE). In the present work, we analyzed whether this increased production of IL-10 contributed to the abnormal production of immunoglobulins (Ig) and of autoantibodies in SLE. The role of IL-10 was compared with that of IL-6, another cytokine suspected to play a role in these abnormalities. The spontaneous in vitro production of IgM, IgG, and IgA by peripheral blood mononuclear cells from SLE patients was weakly increased by recombinant IL (rIL)-6, but strongly by rIL-10. This production was not significantly affected by an anti-IL-6 mAb but was decreased by an anti-IL-10 mAb. We then tested the in vivo effect of these antibodies in severe combined immunodeficiency mice injected with PBMC from SLE patients. The anti-IL-6 mAb did not significantly affect the serum concentration of total human IgG and of anti-double-stranded DNA IgG in the mice. In contrast, the anti-IL-10 mAb strongly inhibited the production of autoantibodies, and, to a lesser extent, that of total human IgG. These results indicate that the Ig production by SLE B lymphocytes is largely IL-10 dependent, and that the increased production of IL-10 by SLE B lymphocytes and monocytes may represent a critical mechanism in the emergence of the autoimmune manifestations of the disease.