Peritoneal molecular environment, adhesion formation and clinical implication

Abstract

Whether induced by infection, inflammation, ischemia, and/or surgical injury, peritoneal adhesions are the leading cause of pelvic pain, bowel obstruction and infertility. It is clear that while postsurgical peritoneal wounds heal without adhesions in some patients, others develop severe scarring from seemingly equal procedures; in addition, in the same patient, adhesions can develop at one surgical site and not in another. The mechanisms underlying the predisposition to form adhesions as well as their site specificity are completely unknown. However, a large number of intraperitoneal surgical procedures are performed each day in the USA, and thus many patients are at risk of developing postoperative adhesions. Therefore, understanding of adhesion formation at the molecular level is essential and in the absence of such information, attempts to prevent patients from developing adhesions will remain an empirical process. The unprecedented advancement in molecular biology during the past decade has led to the identification of many biologically active molecules with the potential of regulating inflammatory and immune responses, angiogenesis and tissue remodeling, events that are central to normal peritoneal wound healing and adhesion formation. Although, the insight into their importance in the development of tissue fibrosis has substantially increased, their major roles in peritoneal biological functions and adhesion formation remain at best speculative. This article reviews the clinical implications of adhesions and attempts to highlight some of the key molecules i.e. growth factors, cytokines, chemokines, proteases and extracellular matrix, that are recognized to regulate inflammation, fibrinolysis, angiogenesis, and tissue remodeling, events that are central to peritoneal wound repair and adhesion formation. Finally, the article discusses the potential application and site specific delivery of several active compounds that are developed to alter the local inflammatory and immune response i.e., cytokine/chemokine network, targeted gene delivery and development of a new generation of biomaterials to prevent adhesion formation. Such understanding of peritoneal biology not only assist us to better manage patients with adhesion, but also those with endometriosis and malignant diseases that affect the peritoneal cavity.

The Effect of Immunosuppression on Peritoneal Adhesions Formation After Small Bowel Transplantation in Rats

“…The onset of cellular and tissue injury is associated with remarkably regulated biochemical and morphological reactions that are mediated by both humeral and cellular immune systems [3]. Postoperative peritoneal adhesion formation appears to be caused by a complex local and systemic inflammatory response to tissue injury, ischemia, infection, or inflammation that results in an imbalance between fibrin formation and degradation [16].…”

“…Using a surgically-induced cecal abrasion model in mice, Chung et al [17] demonstrated that Th1 CD4 ϩ ␣␤ cells are critical in the development of peritoneal adhesions and that these activated T cells become the predominant cells in the peritoneal cavity shortly after tissue injury and throughout adhesiogenesis. Several chymokines and cytokines, including interleukin, M-CSF, GM-CSF, and MCP-1, regulate the fibrinolytic process [3]. TGF-␤ has been correlated with excessive extracellular matrix modifications by induction of several proteins such as collagenase activity, fibronectin, and by inhibition of matrix degradation [3].…”

“…Although the mechanism of adhesion formation after abdominal surgery has not been completely understood, it appears to be caused by complex local and systemic inflammatory responses to peritoneal injury. These responses are regulated by various cytokines, chemokines, and proteases that influence fibrinogenesis, fibrinolysis, angiogenesis, and tissue remodeling after surgical injury [3].…”

Peritoneal cytokines and adhesion formation in endometriosis: an inverse association with vascular endothelial growth factor concentration

“…In addition to endometriosis, adhesions appear to be the main cause of morbidity after surgical trauma, peritonitis, pelvic inflammatory disease, and other related disorders. It has become accepted that the development of pelvic adhesions involves inflammatory responses, abrogated fibrinolysis, and the protease/protease inhibitor system, as well as angiogenesis (10)(11)(12)(13). Inflammatory responses that may lead to induction of adhesion formation may primarily depend on the production of proinflammatory cytokines interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF) (10,14,15).…”

“…Most studies have focused on revealing of the mechanism of postsurgical adhesion formation (10)(11)(12)(13), and still little is known about the putative mechanism(s) of their formation in the course of endometriosis. It is plausible that pelvic adhesion formation in patients with endometriosis depends in part on local inflammatory reactions and abrogated angiogenic activity.…”