title: Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus.
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.
authors.affiliation: Departamento de Immunologia y Reumatologia, Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City D.F., Mexico.
authors.forename: L
authors.initials: L
authors.lastname: Llorente
authors.forename: W
authors.initials: W
authors.lastname: Zou
authors.forename: Y
authors.initials: Y
authors.lastname: Levy
authors.forename: Y
authors.initials: Y
authors.lastname: Richaud-Patin
authors.forename: J
authors.initials: J
authors.lastname: Wijdenes
authors.forename: J
authors.initials: J
authors.lastname: Alcocer-Varela
authors.forename: B
authors.initials: B
authors.lastname: Morel-Fourrier
authors.forename: J C
authors.initials: JC
authors.lastname: Brouet
authors.forename: D
authors.initials: D
authors.lastname: Alarcon-Segovia
authors.forename: P
authors.initials: P
authors.lastname: Galanaud
authors.forename: D
authors.initials: D
authors.lastname: Emilie
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007136:Immunoglobulins; D015850:Interleukin-6; D011994:Recombinant Proteins; D016753:Interleukin-10