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Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus

(1998) JOURNAL OF EXPERIMENTAL MEDICINE. 188(5). p.985-990
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Abstract
Pristane induces a lupus-like syndrome in nonautoimmune mice characterized by the development of glomerulonephritis and lupus-associated autoantibodies. This is accompanied by overproduction of interleukin (IL)-6, a cytokine linked with autoimmune phenomena. The goal of this study was to evaluate the role of IL-6 in autoantibody production in pristane-induced lupus. BALB/cAn IL-6-deficient (-/-) and -intact (+/+) mice were treated with pristane or phosphate-buffered saline, and autoantibody production was evaluated. Pristane induced high levels of immunoglobulin (Ig)G anti-single-stranded DNA, -double-stranded (ds)DNA, and -chromatin antibodies in IL-6(+/+), but not IL-6(-/-) mice by enzyme-linked immunosorbent assay. High titer IgG anti-dsDNA antibodies also were detected in sera from +/+, but not -/-, mice by Crithidia luciliae kinetoplast staining. The onset of IgG anti-dsDNA antibody production in +/+ mice occurred >5 mo after pristane treatment, well after the onset of nephritis, suggesting that these antibodies are not directly responsible for inducing renal disease. In contrast to anti-DNA, the frequencies of anti-nRNP/Sm and anti-Su antibodies were similar in pristane-treated IL-6(-/-) and IL-6(+/+) mice. However, levels were higher in the +/+ group. These results suggest that IgG anti-DNA and chromatin antibodies in pristane-treated mice are strictly IL-6 dependent, whereas induction of anti-nRNP/Sm and Su autoantibodies is IL-6 independent. The IL-6 dependence of anti-DNA, but not anti-nRNP/Sm, may have implications for understanding the patterns of autoantibody production in lupus. Anti-DNA antibodies are produced transiently, mainly during periods of disease activity, whereas anti-nRNP/Sm antibody levels are relatively insensitive to disease activity. This may reflect the differential IL-6 dependence of the two responses.
Keywords
antinuclear antibodies, interleukin 6, anti-DNA antibodies, pristane, systemic lupus erythematosus, B-CELLS, IL-6, IMMUNE-COMPLEX GLOMERULONEPHRITIS, T-CELL CLONES, BALB/C MICE, MURINE LUPUS, MRL/LPR MICE, LPR/LPR MICE, CD40 LIGAND, LPR MICE

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Citation

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Chicago
Richards, HB, M Satoh, M Shaw, Claude Libert, V Poli, and WH Reeves. 1998. “Interleukin 6 Dependence of anti-DNA Antibody Production: Evidence for Two Pathways of Autoantibody Formation in Pristane-induced Lupus.” Journal of Experimental Medicine 188 (5): 985–990.
APA
Richards, H., Satoh, M., Shaw, M., Libert, C., Poli, V., & Reeves, W. (1998). Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus. JOURNAL OF EXPERIMENTAL MEDICINE, 188(5), 985–990.
Vancouver
1.
Richards H, Satoh M, Shaw M, Libert C, Poli V, Reeves W. Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus. JOURNAL OF EXPERIMENTAL MEDICINE. 1998;188(5):985–90.
MLA
Richards, HB, M Satoh, M Shaw, et al. “Interleukin 6 Dependence of anti-DNA Antibody Production: Evidence for Two Pathways of Autoantibody Formation in Pristane-induced Lupus.” JOURNAL OF EXPERIMENTAL MEDICINE 188.5 (1998): 985–990. Print.
@article{1203246,
  abstract     = {Pristane induces a lupus-like syndrome in nonautoimmune mice characterized by the development of glomerulonephritis and lupus-associated autoantibodies. This is accompanied by overproduction of interleukin (IL)-6, a cytokine linked with autoimmune phenomena. The goal of this study was to evaluate the role of IL-6 in autoantibody production in pristane-induced lupus. BALB/cAn IL-6-deficient (-/-) and -intact (+/+) mice were treated with pristane or phosphate-buffered saline, and autoantibody production was evaluated. Pristane induced high levels of immunoglobulin (Ig)G anti-single-stranded DNA, -double-stranded (ds)DNA, and -chromatin antibodies in IL-6(+/+), but not IL-6(-/-) mice by enzyme-linked immunosorbent assay. High titer IgG anti-dsDNA antibodies also were detected in sera from +/+, but not -/-, mice by Crithidia luciliae kinetoplast staining. The onset of IgG anti-dsDNA antibody production in +/+ mice occurred {\textrangle}5 mo after pristane treatment, well after the onset of nephritis, suggesting that these antibodies are not directly responsible for inducing renal disease. In contrast to anti-DNA, the frequencies of anti-nRNP/Sm and anti-Su antibodies were similar in pristane-treated IL-6(-/-) and IL-6(+/+) mice. However, levels were higher in the +/+ group. These results suggest that IgG anti-DNA and chromatin antibodies in pristane-treated mice are strictly IL-6 dependent, whereas induction of anti-nRNP/Sm and Su autoantibodies is IL-6 independent. The IL-6 dependence of anti-DNA, but not anti-nRNP/Sm, may have implications for understanding the patterns of autoantibody production in lupus. Anti-DNA antibodies are produced transiently, mainly during periods of disease activity, whereas anti-nRNP/Sm antibody levels are relatively insensitive to disease activity. This may reflect the differential IL-6 dependence of the two responses.},
  author       = {Richards, HB and Satoh, M and Shaw, M and Libert, Claude and Poli, V and Reeves, WH},
  issn         = {0022-1007},
  journal      = {JOURNAL OF EXPERIMENTAL MEDICINE},
  keyword      = {antinuclear antibodies,interleukin 6,anti-DNA antibodies,pristane,systemic lupus erythematosus,B-CELLS,IL-6,IMMUNE-COMPLEX GLOMERULONEPHRITIS,T-CELL CLONES,BALB/C MICE,MURINE LUPUS,MRL/LPR MICE,LPR/LPR MICE,CD40 LIGAND,LPR MICE},
  language     = {eng},
  number       = {5},
  pages        = {985--990},
  title        = {Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus},
  url          = {http://jem.rupress.org/content/188/5/985.abstract},
  volume       = {188},
  year         = {1998},
}

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