Role of IL-18 in pathogenesis of endometriosis.
BACKGROUND
Endometriosis is a complex disease associated with a wide range of immune responses, including pain, adhesion, exudation of peritoneal fluid, elevation of cytokine levels and generation of autoantibodies. Interleukin (IL)-18 is a strong pleiotropic cytokine known to be involved in various immune diseases. The aim of this study is to elucidate the role of IL-18 in the pathogenesis of endometriosis.


METHODS
IL-18 and IL-1beta concentrations were measured in the peritoneal fluid and sera of 39 endometriosis patients and 15 control women. Expression of IL-18 and IL-18 receptor alpha-chain (IL-18Ralpha) was analysed in endometriotic tissues immunohistochemically. The effects of IL-18 on cyclooxygenase (COX)-II gene expression were analysed in peritoneal fluid monocytes and endometriotic cells of endometriosis patients.


RESULTS
IL-18 concentrations in the peritoneal fluid of endometriosis patients averaged 592.57 +/- 108.27 pg/ml, significantly higher than 260.50 +/- 55.88 pg/ml in non-endometriotic samples. IL-18 concentrations in the serum did not differ significantly between endometriosis and control patients. Similarly, no significant differences were observed in IL-1beta concentrations in either the peritoneal fluid or the serum. IL-18 and IL-18Ralpha were expressed in endometriotic tissues. IL-18Ralpha expression was also observed in cells infiltrating into the inflammatory area of the endometriosis patients. COX-II was induced in peritoneal fluid monocytes and in endometriotic cells in response to IL-18 stimulation.


CONCLUSIONS
The elevation of IL-18 in the peritoneal fluid of endometriosis patients and the induction of COX-II in peritoneal monocytes by IL-18 suggest that IL-18 plays a pathogenic role in endometriosis.
Department of Obstetrics and Gynecology, Institute for Advanced Medical Sciences, Japan.
H
H
Oku
Y
Y
Tsuji
S-I
SI
Kashiwamura
S
S
Adachi
A
A
Kubota
H
H
Okamura
K
K
Koyama
D000328:Adult; D001202:Ascitic Fluid / Q000737:chemistry; D051546:Cyclooxygenase 2; D004715:Endometriosis / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D053727:Interleukin-18 Receptor alpha Subunit; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053724:Receptors, Interleukin-18; D020133:Reverse Transcriptase Polymerase Chain Reaction
C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D007527:Isoenzymes; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases