Tumour necrosis factor α concentrations in the peritoneal fluid of infertile women with minimal or mild endometriosis are lower in patients with red lesions only than in patients without red lesions

Abstract

Tumour necrosis factor alpha (TNFalpha) of peritoneal fluid is believed to have important pro-inflammatory and angiogenic activities in the complex mechanisms of development of peritoneal endometriotic lesions. We have evaluated the concentrations of TNFalpha and macrophages in peritoneal fluid of infertile women with minimal or mild endometriosis and related them to the presence of peritoneal red lesions alone (red lesions only group; n = 11) or their absence (non-red lesions group; n = 36). A group of 39 infertile normo-ovulatory patients with normal pelvic anatomy was used as controls. TNFalpha concentrations did not differ between controls and either group of patients. Patients with red lesions only had significantly lower concentrations of TNFalpha in peritoneal fluid (P < 0.05) and had a higher proportion of samples with undetectable concentrations (P < 0.05) than patients without red lesions. The significant difference in TNFalpha concentrations was present when comparing the groups of patients in the proliferative phase but not in the secretory phase. Macrophage concentrations were not different in the groups. Our findings are compatible with an impairment of macrophage function and therefore lend support to the theory that an inappropriate immunological response of the peritoneal environment to regurgitated endometrium may play a part in the initial phases of endometriotic implants.

Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis

“…We chose to study PDGF, VEGF, IL‐6, RANTES, IL1‐β, IL‐8, TNF‐α, MCP‐1, sFas, and sFasL, as they have been implicated in the possible pathogenesis of endometriosis. In agreement with other studies, we have found a significantly higher concentration of IL‐8, 5,6,12 IL‐6 14,15 and MCP‐1 16–18 in the PF of women with active endometriosis. However, we did not find an equivalent increase in the concentration of these cytokines in the serum of these women, compared to the control group.…”

“…The dynamic interplay among cytokines may contribute in the creation of a microenvironment which favors the implantation of endometrial cells and the progression of the disease. Numerous authors have studied the presence and role of various cytokines in the serum and PF of women with endometriosis 5–10 . Available data in the literature however, have not been consistent.…”

“…The role of peritoneal fluid (PF) cellular population and soluble factors has been studied extensively and these are considered to contribute to the implantation and progression of endometriosis. The endometriosis‐associated inflammatory response, tissue repair and neo‐vascularization are dependent on the PF macrophages and their secretory products (cytokines) 5 . Cytokines are diverse proteins that play a central role in regulating cell proliferation, activation, motility, adhesion, chemotaxis and morphogenesis.…”

Is Endometriosis Associated with Systemic Subclinical Inflammation?

“…Iwabe et al [13] demonstrated that TNF-␣ stimulates proliferation of endometriotic stromal cells through induction of IL-8 gene and protein expression and concluded, that TNF-␣ may be one of the essential factors for the pathogenesis of endometriosis. It has been shown [12,35] , that in women with endometriosis, peritoneal fl uid TNF-␣ concentrations correlate with the stage of the disease. Additionally, several studies reported signifi cantly higher TNF-␣ serum levels in patients with endometriosis compared to the control group, especially in early stages of the disease pointing out an involvement and a role played by acute infl ammatory processes at these early stages [15,36] .…”

Different concentrations of interleukins in the peritoneal fluid of women with endometriosis: relationships with lymphocyte subsets

“…Several studies have suggested that the immune system plays a pivotal role in the pathogenesis and progression of this disease in humans [2][3][4][5] . Although many authors have described a correlation between the endometriosis-associated inflammatory response and peritoneal fluid macrophage-dependent secretion of interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF) [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] , the characteristics of peritoneal fluid mononuclear cell patterns and the types of lymphokine primarily involved in the pathogenesis of endometriosis remain controversial 25 .…”