Characterization of synthetic lung surfactant activity against proinflammatory cytokines in human monocytes

Our previous study demonstrated that the smallest synthetic peptide with the sequence CPVHLKRLLLLLLLLLLLLLLLL, SP-CL16(6-28), admixed with phospholipid (synthetic lung surfactant, SLS) showed strong surface activity. In this study, we attempted to develop a dual-type surfactant with both anti inflammatory and surface activities. SP-CL16(6-28) was first chemically synthesized and then purified for use by centrifugal partition chromatography. A mixture of SP-CL16(6-28) and phospholipid complex was tested for anti inflammatory activity using the human monocyte cell line THP-1. Whether the suppression of tumor necrosis factor-alpha (TNF-a), interleukin (IL)-8, IL-6, IL-1beta, and macrophage migration inhibitory factor (MIF) was reduced by lipopolysaccharide (LPS) in monocytes was examined. Levels of these cytokines were measured by enzyme-linked immunosorbent assay. It was found that SLS significantly and dose dependently inhibited the secretion of TNF-alpha by THP-1 cells following stimulation with LPS. Dipalmitoylphosphatidylcoline did not inhibit the release of cytokines. These findings suggest that SLS has anti inflammatory activity. Therefore it should be possible to develop a SLS with both anti inflammatory activity and surface activity.