Chlorpromazine, procainamide and hydralazine produced a murine autoimmune disease resembling human lupus (48.31)

Abstract

Abstract Chlorpromazine, procainamide and hydralazine have indeed been implicated in producing a human lupus-like disorder. These drugs induce the formation of a phospholipid arrangement different to the lipid bilayer called non-bilayer phospholipid arrangement (NPA). Since these drugs form NPA in liposomes and cultured cells, it is possible that these drugs can stabilize NPA structures in cell membranes producing an abnormal NPA exposure, perhaps facilitating the subsequent production of specific antibodies. To evaluate this potential role of NPA inductors, the drugs alone or drug-induced NPA were administered to BALB/c mice. We observed that 30-45% of mice treated with NPA inductors and 55-60% treated with drug-induced NPA, produced anti-NPA antibodies. These antibodies appeared 4 weeks prior to anti-cardiolipin, anticoagulant, anti-histone and anti-nuclear antibodies. Mice presented some areas of the face with alopecia, the histopathology of these areas showed similar changes to those found in human lupus skin lesions. Dense inflammatory infiltrate in dermis with deposition of immune complexes in dermal-epidermal junction and also along the basement membrane of glomerular capillaries were observed. This model of lupus might contribute to a better understanding of the immunological basis of human lupus and probably toward the development of better human therapeutic strategies.