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.