Enhanced prostaglandin E2 production by monocytes in atopic dermatitis (AD) is not accompanied by enhanced production of IL-6, IL-10 or IL-12.
AD is associated with a bias of the T helper cells to show increased IL-4 and reduced interferon-gamma (IFN-gamma) production. The production of IFN-gamma and IL-4 and the development of Th cells into either high IFN-gamma or high IL-4 producers is strongly influenced by factors produced by antigen-presenting cells (APC), like IL-12 and prostaglandin E2 (PGE2). IL-12 selectively enhances IFN-gamma production and favours the development of IFN-gamma-producing Th cells, whereas PGE2 selectively inhibits IFN-gamma production by Th cells. The aim of this study was to test whether the increased IL-4/IFN-gamma production ratio by Th cells in AD can be explained by an increased PGE2/IL-12 production ratio by the APC. Monocytes were used as APC source. PGE2 and IL-12 production by lipopolysaccharide (LPS)-stimulated monocytes from 12 AD patients and 12 non-atopic controls was determined using two complementary experimental systems, whole blood cultures and purified monocytes. In addition, we determined IL-6 production as a measure of monocyte activation, and IL-10 production because IL-12 production by monocytes is highly influenced by endogenously produced IL-10. The monocytes from AD patients showed normal production levels of IL-6 and IL-10, a two-fold, but non-significant decrease in IL-12 production, and a significantly (three-fold) higher PGE2 production than those from non-atopic controls. Here we show for the first time that enhanced PGE2 production by monocytes in AD is not accompanied by a general rise in cytokine production. We conclude that AD is indeed associated with an increased PGE2/IL-12 production ratio by monocytes.
Snijders
A
A
Laboratory of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, The Netherlands.
Van der Pouw Kraan
T C
TC
Engel
M
M
Wormmeester
J
J
Widjaja
P
P
Zonneveld
I M
IM
Bos
J D
JD
Kapsenberg
M L
ML
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000097:blood*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D007378:Interleukins / Q000096:biosynthesis* / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D013268:Stimulation, Chemical
D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D015232:Dinoprostone