Advertisement

Differences in the Induction of Autoimmune Responses in A.SW/SnJ Mice by Various Agents

  • X. Joseph
  • C. J. G. Robinson
  • A. A. Abraham
  • T. Balazs
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 9)

Abstract

Susceptibility to certain drug-induced immunological reactions is under the genetic control of the major histocompatibility complex (MHC). Previously, ten inbred murine strains bearing different H-2 (murine MHC) haplotypes were screened for autoimmune responses to HgC12, gold sodium thiomalate (GST) and D-penicillamine. Only one of these strains, A.SW/SnJ (H-2s), developed antinuclear antibodies (ANA) in response to treatment with all three agents. In the present study the ability of this strain to develop ANA in response to treatment with procainamide (P) and hydralazine (H), two drugs which frequently induce ANA in humans, was examined Groups of 4-to 5-month-old A.SW/SnJ and C3H/HeSnJ (a resistant strain) mice of both sexes were given daily P (200 mg/kg) or H (40 mg/kg) in drinking water, or GST weekly (10 mg/kg im; positive control) with appropriate controls. After 4 months of treatment, A.SW mice were given the lipid A portion of lipopolysaccharide (Lipid A-LPS), a polyclonal B cell activator, 25 μg ip twice weekly for an additional 4 months along with the drug treatments. Induction of ANA occurred only in GST-treated A.SW/SnJ mice, regardless of Lipid A-LPS treatment. These results suggest that the H-2 controlled sensitivity of A.SW strain is antigen-specific.

Key words

Major histocompatibility complex Mercury chloride Gold sodium thiomalate d-penicillamine Hydralazine Procainamide Autoimmunity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Balazs T, Robinson CJG (1983) Procainamide-induced antinuclear antibodies in beagle dogs. Toxicol Appl Pharmacol 71: 299–302PubMedCrossRefGoogle Scholar
  2. Balazs T, Robinson CJG, Balter N (1981) Hydralazine-induced antinuclear antibodies in beagle dogs. Toxicol Appl Pharmacol 57: 452–456PubMedCrossRefGoogle Scholar
  3. Batchelor JR, Welsh KI, Tinoco RM, Dollery CT, Hughes GRV, Bernstein R, Ryan P, Naish PF, Aber GM, Bing RF, Russell GI (1980) Hydralazine-induced systemic lupus erythematosus: Influence of HLA-DR and sex on susceptibility. Lancet 1: 1107–1109PubMedCrossRefGoogle Scholar
  4. Hang L, Slack JH, Amundson C, Izui S, Theofilopoulos AN, Dixon FJ (1983) Induction of murine autoimmune disease by chronic polyclonal B cell activation. J Exp Med 157:874–883PubMedCrossRefGoogle Scholar
  5. Lee SL, Chase PH (1975) Drug-induced systemic lupus erythematosus: A critical review. Semin Arthritis Rheum 5: 83–103PubMedCrossRefGoogle Scholar
  6. Robinson CJG, Egorov I, Balazs T (1983) Strain differences in the induction of antinuclear antibodies by mercuric chloride, gold sodium thiomalate and D-penicillamine in inbred mice. Fed Proc 42: 12–13Google Scholar
  7. Wooley PH, Griffin J, Panayi GS, Batchelor JR, Welsh KI, Gibson TJ (1980) HLA-DR antigens and toxic reaction to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis. N Engl J Med 303: 300–302PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • X. Joseph
    • 1
  • C. J. G. Robinson
    • 1
  • A. A. Abraham
    • 1
  • T. Balazs
    • 1
  1. 1.Food and Drug Administration and George Washington UniversityUSA

Personalised recommendations