Role of IL-18 in pathogenesis of endometriosis.

Abstract

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.

• Authors: H Oku, Y Tsuji, S-I Kashiwamura, S Adachi, A Kubota, H Okamura, K Koyama
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 19 Issue 3 Pg. 709-14 (Mar 2004) ISSN: 0268-1161 [Print] England
• PMID: 14998974 (Publication Type: Journal Article)

Chemical References

• IL18R1 protein, human
• Interleukin-18
• Interleukin-18 Receptor alpha Subunit
• Isoenzymes
• Membrane Proteins
• Protein Isoforms
• RNA, Messenger
• Receptors, Interleukin
• Receptors, Interleukin-18
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases

Topics

• Adult
• Ascitic Fluid (chemistry)
• Cyclooxygenase 2
• Endometriosis (blood, etiology, metabolism, pathology)
• Enzyme Induction
• Female
• Humans
• Immunohistochemistry
• Interleukin-18 (analysis, genetics, metabolism, pharmacology)
• Interleukin-18 Receptor alpha Subunit
• Isoenzymes (biosynthesis, metabolism)
• Membrane Proteins
• Middle Aged
• Prostaglandin-Endoperoxide Synthases (biosynthesis, metabolism)
• Protein Isoforms (metabolism)
• RNA, Messenger (metabolism)
• Receptors, Interleukin (genetics, metabolism)
• Receptors, Interleukin-18
• Reverse Transcriptase Polymerase Chain Reaction