Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo.
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.
Yung
R
R
University of Michigan, Ann Arbor, and the Ann Arbor Veterans Administration Hospital, 48109-0531, USA.
Chang
S
S
Hemati
N
N
Johnson
K
K
Richardson
B
B
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
D001323:Autoantibodies; D016169:Lymphocyte Function-Associated Antigen-1; D006830:Hydralazine; D011342:Procainamide; D006918:Hydroxyurea