he skin serves an important role in the defense mechanism against pathogens and possesses immunomodulatory functions. Several in vitro models that mimic different aspects of local skin inflammation exists. The use of ex vivo human skin organ culture had been reported previously. However, comprehensive data of the cytokine secretory profile of the system and kinetics have not been reported. The aim of the current study was to investigate the levels of key cytokines secretion upon lipopolysaccharide (LPS) stimuli. First, the skin explants were treated without or with three different LPS subtype and the impact on IL-6 and IL-8 secretion was evaluated. All LPS compounds enhance the two cytokine secreted levels in a dose-dependent manner. However, efficacy and potency differed. Next, a kinetic multiplex analysis was performed on LPS (E.coli O111:B4)-stimulated explants, taken from three different skin donors. Cytokine secretion pattern during 72 hr period was recorded. The levels of the pro-inflammatory cytokines IL-6, IL-8, TNFα, IL-1β were affected by LPS stimuli, but with differential secretion pattern. In addition, the anti-inflammatory cytokine IL-10 was also enhanced in the system, suggesting an auto-regulatory prosses. IL-1α and IL-15 showed donor-specific changes. Lastly, dexamethasone attenuated cytokine secretion in five independent repetitions, re-enforcing the ability of the system to be used as a drug screening platform.

Ex-vivo cytokine secretion pattern of LPS-induced inflammation in human skin explants