The underlying mechanisms of skin inflammation in atopic dermatitis

The underlying mechanisms of skin inflammation in atopic dermatitis (AD) are not completely understood but inflammatory cell activation and dysregulated cytokine production appear to play a critical role in pathogenesis of AD. Inducible nitric oxide synthase (iNOS) is expressed by dermal endothelial cells and perivascular inflammatory cells in the atopic skin lesion, suggesting the involement of nitric oxide (NO) in the skin inflammation of AD. Among the proinflamatory cytokines interferon-gamma (IFN-) is the most efficient inducer of NO production. The purpose of the study was to examine IFN- and NO plasma levels in patients with AD. We have also measured NO production by mononuclear (MN) and polymorphonuclear (PMN) leucocytes in cells culture systems. Seventeen patients with atopic dermatitis and ten healthy volunteers were included in this study. NO plasma levels of patients with AD were significantly increased (p=0.001) as compared to nonatopic controls. No significant difference in NO levels in MN cells cultures of AD patients and nonatopic controls was observed (p=0.083). NO levels in PMN cells cultures of AD patients were significantly higher (p=0.011). IFN- plasma concentration in AD patients was significantly increased as compared to nonatopic controls (p=0.005). Our results suggest that PMN leucocytes in AD patients could be source of increased NO plasma levels in patients with AD. As our patients have lasting eczematous skin lesions, our results also lend support to the two-phase-model for the pathogenesis of AD were in a second phase expresion of Th-1 cytokines, such as IFN-, predominates.