title: Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo.
abstract: OBJECTIVE
  T cells treated with DNA methylation inhibitors overexpress lymphocyte function-associated antigen 1 (LFA-1), which results in autoreactivity, and the autoreactive cells cause a lupus-like disease in vivo, suggesting a mechanism by which some agents may cause drug-induced lupus. This study compared the effects of procainamide (Pca) and hydralazine (Hyd) with those of structural analogs, to determine if the degree of LFA-1 overexpression and T cell autoreactivity correlated with the ability of the agents to induce autoimmunity.
  
  
  METHODS
  Cloned murine T helper 2 cells were treated with Pca, N-acetylprocainamide, Hyd, Phthalazine, or hydroxyurea (HU). The treated cells were then compared for LFA-1 overexpression, autoreactivity, and the ability to induce autoimmunity in vivo.
  
  
  RESULTS
  Pca and Hyd were more potent than their analogs or HU in all 3 assays.
  
  
  CONCLUSIONS
  The results support a relationship between LFA-1 overexpression, T cell autoreactivity, and autoimmunity, and suggest a mechanism by which Pca and Hyd, but not the analogs, may cause drug-induced lupus.
authors.affiliation: University of Michigan, Ann Arbor, and the Ann Arbor Veterans Administration Hospital, 48109-0531, USA.
authors.forename: R
authors.initials: R
authors.lastname: Yung
authors.forename: S
authors.initials: S
authors.lastname: Chang
authors.forename: N
authors.initials: N
authors.lastname: Hemati
authors.forename: K
authors.initials: K
authors.lastname: Johnson
authors.forename: B
authors.initials: B
authors.lastname: Richardson
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006830:Hydralazine / Q000009:adverse effects; D006918:Hydroxyurea / Q000009:adverse effects; D008177:Lupus Vulgaris / Q000139:chemically induced*; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008814:Mice, Inbred NZB; D011342:Procainamide / Q000009:adverse effects; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D016169:Lymphocyte Function-Associated Antigen-1; D006830:Hydralazine; D011342:Procainamide; D006918:Hydroxyurea