Peptide XIB13 reduces capillary leak in a rodent burn model

• A cingulin-derived peptide to attenuate stress-induced endothelial cytoskeleton disarrangement and to reduce burn-induced edema.

ObjectiveEdema due to capillary leak is a generalized and life threatening event in sepsis and major burns for which there is no causal treatment. Local burn wounds are an ideal model to investigate the impact of a new therapeutic agent on edema formation. We aimed to identify peptide sequences of cingulin that can attenuate stress-induced endothelial cytoskeleton disarrangement in vitro and which reduce burn-induced edema in vivo.MethodsCingulin-derived peptides were screened in high content cell culture assays monitoring actin displacement and endothelial cell/cell contacts. The ears of male hairless mice (n = 44) were inflicted with full thickness burns using a hot air jet. Mice with and without burn injuries were treated with Xib13 or solvent by continuous intraperitoneal application for 3 days. Edema, microcirculation, leukocyte-endothelial interactions and angiogenesis – measured as non-perfused area – were investigated over a 12-day period using intravital fluorescence microscopy.ResultsXib13 reduced endothelial stress formation and stabilized endothelial tight junctions in cell-cultures. In the burn model, Xib13 improved angiogenesis compared to controls (non-perfused area on day 12: 5.7 ± 1.5% vs. 12.0 ± 2.1%; p < 0.05). Edema was significantly reduced at all observation points in Xib13-treated animals as compared to controls (day 12: 67.6 ± 2.6% vs. 83.2 ± 6.4%).ConclusionXib13 improved angiogenesis, reduced edema formation and showed no side effects on other physiological parameters. Since edema formation is a serious parameter for burn conversion and is associated with survival it could provide a new treatment option for patients with burn injuries.