Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus.
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.
Llorente
L
L
Departamento de Immunologia y Reumatologia, Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City D.F., Mexico.
Zou
W
W
Levy
Y
Y
Richaud-Patin
Y
Y
Wijdenes
J
J
Alcocer-Varela
J
J
Morel-Fourrier
B
B
Brouet
J C
JC
Alarcon-Segovia
D
D
Galanaud
P
P
Emilie
D
D
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
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007136:Immunoglobulins; D015850:Interleukin-6; D011994:Recombinant Proteins; D016753:Interleukin-10