Expression of IL-18 mRNA and secretion of IL-18 are reduced in monocytes from patients with atopic dermatitis

Background: IL-18 has been found to be an IFN-gamma -inducing factor that plays an important role in T(H)1 cell activation. Recently, IL-18 has also been found to enhance a T(H)2 cellular response in a specific setting. Objective: The aim of this study was to elucidate the role of monocytes and soluble factors, with special focus on IL-18, in the pathogenesis of atopic dermatitis (AD). Methods: The release of cytokines front PBMCs and purified monocytes was measured through use of ELISA; mRNA expression was evaluated by RT-PCR. The results from patients with AD were compared with those from healthy controls. Results: IL-18 secretion was reduced in both unstimulated and lipopolysaccharide-stimulated monocytes from patients with AD. The mRNA expression of IL-18 and IL-lp-converting enzyme was significantly reduced in unstimulated monocytes from patients with AD (P <.03 and P <.01, respectively). Patients with AD had an elevated secretion of prostaglandin E-2 (PGE(2)) from unstimulated PBMCs (P <.001). The anti-PGE(2) antibody reversed the suppressive effect of PGE(2) on IL-18 secretion in unstimulated PBMCs from patients with AD. Conclusions: Decreased IL-18 production, together with a significantly reduced IL-18 and ICE mRNA expression in unstimulated monocytes and elevated PGE(2) secretion from PBMCs, was associated with the pathogenesis of AD.