Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus.
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.
Richards
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HB
Department of Medicine, Thurston Arthritis Research Center, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill 27599-7280, USA.
Satoh
M
M
Shaw
M
M
Libert
C
C
Poli
V
V
Reeves
W H
WH
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology; D002843:Chromatin / Q000276:immunology; D004247:DNA / Q000276:immunology*; D004277:DNA, Single-Stranded / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000502:physiology*; D008181:Lupus Nephritis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D013729:Terpenes / Q000633:toxicity*; D055517:snRNP Core Proteins
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D002843:Chromatin; D004277:DNA, Single-Stranded; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; D017411:Ribonucleoproteins, Small Nuclear; D013729:Terpenes; D055517:snRNP Core Proteins; C009042:pristane; D004247:DNA