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 from 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-1 beta-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.
Higashi
N
N
Department of Dermatology, Marselisborg Hospital, University of Aarhus, Denmark.
Gesser
B
B
Kawana
S
S
Thestrup-Pedersen
K
K
D000293:Adolescent; D000328:Adult; D020170:Caspase 1 / Q000096:biosynthesis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D020382:Interleukin-18; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D016753:Interleukin-10; D020170:Caspase 1; D015232:Dinoprostone