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J Exp Med. Mar 1, 1995; 181(3): 839–844.
PMCID: PMC2191898

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Klinman DM, Steinberg AD. Systemic autoimmune disease arises from polyclonal B cell activation. J Exp Med. 1987 Jun 1;165(6):1755–1760. [PMC free article] [PubMed]
  • Handwerger BS. Lymphocyte biology in lupus. Curr Opin Rheumatol. 1990 Oct;2(5):749–761. [PubMed]
  • Block SR, Gibbs CB, Stevens MB, Shulman LE. Delayed hypersensitivity in systemic lupus erythematosus. Ann Rheum Dis. 1968 Jul;27(4):311–318. [PMC free article] [PubMed]
  • Morimoto C, Steinberg AD, Letvin NL, Hagan M, Takeuchi T, Daley J, Levine H, Schlossman SF. A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody. J Clin Invest. 1987 Mar;79(3):762–768. [PMC free article] [PubMed]
  • Via CS, Tsokos GC, Bermas B, Clerici M, Shearer GM. T cell-antigen-presenting cell interactions in human systemic lupus erythematosus. Evidence for heterogeneous expression of multiple defects. J Immunol. 1993 Oct 1;151(7):3914–3922. [PubMed]
  • Rousset F, Garcia E, Defrance T, Péronne C, Vezzio N, Hsu DH, Kastelein R, Moore KW, Banchereau J. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1890–1893. [PMC free article] [PubMed]
  • de Waal Malefyt R, Yssel H, de Vries JE. Direct effects of IL-10 on subsets of human CD4+ T cell clones and resting T cells. Specific inhibition of IL-2 production and proliferation. J Immunol. 1993 Jun 1;150(11):4754–4765. [PubMed]
  • Enk AH, Angeloni VL, Udey MC, Katz SI. Inhibition of Langerhans cell antigen-presenting function by IL-10. A role for IL-10 in induction of tolerance. J Immunol. 1993 Sep 1;151(5):2390–2398. [PubMed]
  • Llorente L, Richaud-Patin Y, Wijdenes J, Alcocer-Varela J, Maillot MC, Durand-Gasselin I, Fourrier BM, Galanaud P, Emilie D. Spontaneous production of interleukin-10 by B lymphocytes and monocytes in systemic lupus erythematosus. Eur Cytokine Netw. 1993 Nov-Dec;4(6):421–427. [PubMed]
  • Llorente L, Richaud-Patin Y, Fior R, Alcocer-Varela J, Wijdenes J, Fourrier BM, Galanaud P, Emilie D. In vivo production of interleukin-10 by non-T cells in rheumatoid arthritis, Sjögren's syndrome, and systemic lupus erythematosus. A potential mechanism of B lymphocyte hyperactivity and autoimmunity. Arthritis Rheum. 1994 Nov;37(11):1647–1655. [PubMed]
  • Ishida H, Muchamuel T, Sakaguchi S, Andrade S, Menon S, Howard M. Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice. J Exp Med. 1994 Jan 1;179(1):305–310. [PMC free article] [PubMed]
  • Nagafuchi H, Suzuki N, Mizushima Y, Sakane T. Constitutive expression of IL-6 receptors and their role in the excessive B cell function in patients with systemic lupus erythematosus. J Immunol. 1993 Dec 1;151(11):6525–6534. [PubMed]
  • Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. [PubMed]
  • Guzmán J, Cardiel MH, Arce-Salinas A, Sánchez-Guerrero J, Alarcón-Segovia D. Measurement of disease activity in systemic lupus erythematosus. Prospective validation of 3 clinical indices. J Rheumatol. 1992 Oct;19(10):1551–1558. [PubMed]
  • Emilie D, Wijdenes J, Gisselbrecht C, Jarrousse B, Billaud E, Blay JY, Gabarre J, Gaillard JP, Brochier J, Raphael M. Administration of an anti-interleukin-6 monoclonal antibody to patients with acquired immunodeficiency syndrome and lymphoma: effect on lymphoma growth and on B clinical symptoms. Blood. 1994 Oct 15;84(8):2472–2479. [PubMed]
  • Nisitani S, Tsubata T, Murakami M, Okamoto M, Honjo T. The bcl-2 gene product inhibits clonal deletion of self-reactive B lymphocytes in the periphery but not in the bone marrow. J Exp Med. 1993 Oct 1;178(4):1247–1254. [PMC free article] [PubMed]
  • Levy Y, Brouet JC. Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. J Clin Invest. 1994 Jan;93(1):424–428. [PMC free article] [PubMed]
  • Emilie D, Touitou R, Raphael M, Peuchmaur M, Devergnee O, Rea D, Coumbraras J, Crevon MC, Edelman L, Joab I, et al. In vivo production of interleukin-10 by malignant cells in AIDS lymphomas. Eur J Immunol. 1992 Nov;22(11):2937–2942. [PubMed]
  • Emilie D, Fior R, Llorente L, Marfaing-Koka A, Peuchmaur M, Devergne O, Jarrousse B, Wijdenes J, Boue F, Galanaud P. Cytokines from lymphoid organs of HIV-infected patients: production and role in the immune disequilibrium of the disease and in the development of B lymphomas. Immunol Rev. 1994 Aug;140:5–34. [PubMed]
  • O'Garra A, Chang R, Go N, Hastings R, Haughton G, Howard M. Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10. Eur J Immunol. 1992 Mar;22(3):711–717. [PubMed]
  • Ishida H, Hastings R, Kearney J, Howard M. Continuous anti-interleukin 10 antibody administration depletes mice of Ly-1 B cells but not conventional B cells. J Exp Med. 1992 May 1;175(5):1213–1220. [PMC free article] [PubMed]
  • Lin H, Mosmann TR, Guilbert L, Tuntipopipat S, Wegmann TG. Synthesis of T helper 2-type cytokines at the maternal-fetal interface. J Immunol. 1993 Nov 1;151(9):4562–4573. [PubMed]
  • Ullrich SE. Mechanism involved in the systemic suppression of antigen-presenting cell function by UV irradiation. Keratinocyte-derived IL-10 modulates antigen-presenting cell function of splenic adherent cells. J Immunol. 1994 Apr 1;152(7):3410–3416. [PubMed]
  • Mills JA. Systemic lupus erythematosus. N Engl J Med. 1994 Jun 30;330(26):1871–1879. [PubMed]

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