ABSTRACT
Cytokines are important mediators of intercellular communication within the immune system. They target a variety of cells and show proliferative, chemoattractant, differentiative, or cytostatic effects. Most cytokines are coupled to intracellular signaling and second-messenger pathways with the help of high-affinity receptors on target cell membranes.1-4
Immune system mediators such as cytokines and chemokines have important roles in the pathogenesis of endometriosis, which is associated with an inflammatory peritoneal environment. Macrophages, at 85% (between 0.4 and 1.6×106 cells/mL), constitute the majority of cells within the peritoneal cavity5,6 (Figure 7.1). Others include eosinophils, mast cells, lymphocytes, and mesothelial cells. Endometriosis patients have increased numbers of activated macrophages compared to healthy controls.7 These cells secret various local products, such as growth factors
and cytokines. The following cytokines and growth factors are important inflammatory mediators in the peritoneal fluid of patients with endometriosis:interleukins IL-1, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, RANTES (regulated upon activation, normal T cell-expressed and secreted), eotaxin, TNF-α (tumor necrosis factor-α), IFN-γ (interferonγ), ENA-78 (epithelial neutrophil-activating protein-78), MCP-1 (monocyte chemotactic protein), EGF (epidermal growth factor), IGF (insulin-like growth factor), TGF-β (transforming growth factor-β), CSF (colony-stimulating factor), PDGF (platelet-derived growth factor), and VEGF (vascular endothelial growth factor). Usually, levels correlate with the severity of the disease, with the highest amounts of cytokines being present in advanced stages of endometriosis. Other cytokines are not different between endometriosis and control patients without disease; some are decreased in endometriosis patients8-38 (Table 7.1). Cytokines are produced not only by immune cells, but also by endometriotic implants themselves. Supposedly, they play a role in the development and progression of endometriosis as well as in endometriosis-associated infertility.39 Oocyte maturation, sperm mobility, sperm-egg interaction, embryo development, and implantation might be compromised by an imbalance of cytokines and growth factors.4046 Cytokines are paracrine mediators for steroid hormone actions. They have to be very precisely regulated within the tissue microenvironment owing to their potency in relatively low concentrations (high pM concentrations).47
