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

J Exp Med. 1995 Mar 1;181(3):839-44. doi: 10.1084/jem.181.3.839.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal / immunology
  • Autoantibodies / biosynthesis*
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Female
  • Humans
  • Immunoglobulins / biosynthesis
  • Interleukin-10 / pharmacology
  • Interleukin-10 / physiology*
  • Interleukin-6 / pharmacology
  • Interleukin-6 / physiology
  • Lupus Erythematosus, Systemic / immunology*
  • Mice
  • Mice, SCID
  • Middle Aged
  • Recombinant Proteins / pharmacology

Substances

  • Antibodies, Monoclonal
  • Autoantibodies
  • Immunoglobulins
  • Interleukin-6
  • Recombinant Proteins
  • Interleukin-10