Roflumilast

Roflumilast displays anti-inflammatory and immunomodulatory in vitro. Roflumilast inhibits LTB4 synthesis in human neutrophil with IC50 of 2 nM. Roflumilast inhibits fMLP-stimulated ROS formation as luminol-enhanced CL in human neutrophils or eosinophils with IC35 of 4 nM, and 7 nM, repectively. Roflumilast inhibits LPS-stimulated TNF-α synthesis in monocytes with IC40 of 21 nM. Roflumilast inhibits TNF-α synthesis in monocyte-derived dendritic cells with IC20 of 5 nM. Rolfumilast inhibits anti-CD3 and anti-CD28 antibody-stimulated proliferation of CD4+ T cells with IC30 of 7 nM. Rolfumilast inhibits anti-CD3 and anti-CD28 antibody-stimulated synthesis of IL-2, IL-4, IL-5, and IFN-v in CD4+ T cells with IC20 of 1 nM, IC30 of 7 nM, IC25 of 13 nM, and IC35 of 8 nM, respectively. ^[2]

Roflumilast is activity against pulmonary inflammatory response related to COPD in animal model. Roflumilast (5 mg/kg/day) induces reduction of neutrophils, macrophages, DC, B-cells, CD4⁺ T cells, CD8⁺ T cells in the lung of mice exposed to tobacco smoke for 7 month by 78%, 82%, 48%, 100%, 98%, and 88%, respectively. ^[3] Roflumilast is an efficient inhibitor of lung fibrotic remodeling. Roflumilast dose-dependently diminishes total lung hydroxyproline after bleomycin, attaining about 47% inhibition at 5 mg/kg/day, paralleled by a reduction in lung αI(I) collagen transcripts and fibrotic lesions. Roflumilast reduces oxidative stress in vivo. Roflumilast (5 mg/kg/day) moderately reduces an increase in BAL fluid lipid hydroperoxides measured at day 14 after intratracheal bleomycin administration in mice. ^[4]