Repeated Domperidone treatment modulates pulmonary cytokines in LPS-induced acute lung injury in mice

Abstract The dopaminergic antagonist drug Domperidone has immunomodulatory effects. We investigated the effects of repeated Domperidone treatment in a model of Lypopolyssacharide (LPS)-induced acute lung inflammation. Adult C57BL/6J mice were treated with either Vehicle or Domperidone for 5 days, and challenged intranasally with LPS in the following day. The behavior of mice was analyzed in the open field and elevated plus-maze test before and 24 h after LPS challenge. The bronchoalveolar lavage fluid, blood and lung tissue were collected 24 h and 48 h after LPS challenge. Domperidone treatment increased LPS-induced tumor necrosis factor (TNF) and interleukin (IL)-6 production in the bronchoalveolar lavage fluid, without altering tissue damage and the number of immune cells in the lungs and circulation. Locomotor and anxiety-like behavior were unchanged after Domperidone and/or LPS treatment. Cytokine data indicate that Domperidone promotes a change in activity of other cell types, likely alveolar epithelial cells, without affecting immune cell migration in the present model. Due to the role of these cytokines in progression of inflammation, Domperidone treatment may exacerbate a subsequent inflammatory injury.