Peritoneal fluid cytokines and the relationship with endometriosis and pain

Abstract

It is generally accepted that the current scoring system for endometriosis has little correlation with clinical symptoms such as pain, and therefore we may deduce that either endometriosis does not cause pain, or that the current scoring system does not indicate the biological activity of the disease. Pain may occur because the presence of endometriosis produces an intraperitoneal inflammatory response, and several studies have shown that the cytokine content of peritoneal fluid differs between women with and without endometriosis. We studied the relationship between tumour necrosis factor alpha (TNF alpha), platelet-derived growth factor (PDGF), interleukin (IL)-6, IL-4 and TNF (alpha and beta) activity in peritoneal fluid and the clinical history of pain and infertility. TNF alpha concentrations were increased in peritoneal fluid of women with endometriosis and of infertile women; PDGF concentrations were increased in peritoneal fluid of parous women; IL-6 was increased in peritoneal fluid of women with adhesions; IL-4 was absent from peritoneal fluid. PDGF and IL-6 concentrations were cycle related, with the highest amounts in the menstrual and proliferative phases respectively. We failed to demonstrate any association between concentrations of cytokines in vitro and pain symptoms or severity of endometriosis.

Endometrial-Peritoneal Interactions during Endometriotic Lesion Establishment

“…Tumor necrosis factor (TNF)-␣ and IL-1␤, which up-regulate the inflammatory NF-B pathway, have been found at high levels in the peritoneal fluid from women with endometriosis. 34,35 NF-B was shown to be activated in endometriotic lesions 29 and in peritoneal macrophages from women with endometriosis. 36 Moreover, two inhibitors of the NF-B pathway significantly reduced xenograft development in the nude mouse model of endometriosis.…”

Endometriosis and Angiogenic Factors

“…TNF is able to induce apoptotic cell death, to induce inflammation and to inhibit tumorigenesis and viral replication. It is considered the most representative cytokine involved in the pathogenesis of endometriosis: a clear positive association between the content of TNFin peritoneal fluid and the severity of endometriosis has been demonstrated (Overton et al,1996). Numerous studies indicate that both activated macrophages and the ectopic endometrium itself are responsible for the abnormal production of TNF-in the peritoneal fluid and that this cytokine is involved in the proliferation of endometriotic stromal cells .…”

Is There a Role for Acupuncture in Endometriosis Pain, Or ‘endometrialgia’?

“…Sensitising agents (PGE2, kinins, amines, growth factors, chemokines and cytokines) reduce the threshold level of activation and increase the responsiveness of the terminal by binding to specific receptors expressed on the membrane of the nociceptor terminal. [51][52][53][54] Among these are the transient receptor potential (TRP) channels. The TRP channels have emerged as a family of evolutionarily conserved ligand gated ion channels that contribute to the detection of physical stimuli.…”