Moxifloxacin Inhibits Neutrophil Responses to Immune Complexes and Ameliorates Skin Inflammation in a Model of Pemphigoid Diseases.

Moxifloxacin, a fluoroquinolone antibiotic with immunomodulatory activity, has not been evaluated for effects on autoantibody-driven inflammation. Pemphigoid diseases are a group of autoimmune blistering skin diseases driven by pathogenic autoantibodies and granulocytes. With current treatments for pemphigoid diseases associated with substantial adverse effects, there is a high medical need for new treatment strategies. We investigated the effect of moxifloxacin on skin inflammation in the antibody transfer mouse model of bullous pemphigoid-like epidermolysis bullosa acquisita. Moxifloxacin attenuated skin inflammation in this model markedly. In vitro, moxifloxacin inhibited responses of neutrophils to fixed IgG immune complexes, including the release of leukotriene B4 (LTB4), a lipid mediator essential for disease propagation in this model. Moxifloxacin also reduced the maximal respiration rate of mitochondria and inhibited mitochondrial complex I. Consistent with a hypothetical direct link between mitochondrial complex I actions and the release of LTB4, the mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)-decyltriphenylphosphonium (SkQ1; visomitin) reduced the immune complex-induced release of LTB4 from neutrophils dose-dependently. Collectively, our results demonstrate that moxifloxacin can ameliorate autoantibody-induced granulocytic skin inflammation. The disruption of select mitochondrial functions and of the immune complex-induced release of LTB4 from neutrophils might contribute to these therapeutic effects. Hence, moxifloxacin should be assessed as a drug for the treatment of patients with pemphigoid diseases.