The Innate Immune Response to Secondary Peritonitis

Abstract

Secondary peritonitis continues to cause high morbidity and mortality despite improvements in medical and surgical therapy. This review combines data from published literature, focusing on molecular patterns of inflammation in pathophysiology and prognosis during peritonitis. Orchestration of the innate immune response is essential. To clear the microbial infection, activation and attraction of leukocytes are essential and beneficial, just like the expression of inflammatory cytokines. Exaggeration of these inflammatory systems leads to tissue damage and organ failure. Nonsurvivors have increased proinflammation, complement activation, coagulation, and chemotaxis. In these patients, anti-inflammatory systems are decreased in blood and lungs, whereas the abdominal compartment shows decreased neutrophil activation and decreased or stationary chemokine and cytokine levels. A later down-regulation of proinflammatory mediators with concomitant overexpression of anti-inflammatory mediators leads to immunoparalysis and failure to clear residual bacterial load, resulting in the occurrence of superimposed infections. Thus, in patients with adverse outcome, the inflammatory reaction is no longer contained within the abdomen, and the inflammatory response has shifted to other compartments. For the understanding of the host response to secondary peritonitis, it is essential to realize that the defense systems presumably are expressed differently and, in part, autonomously in different compartments.

Dps and DpsL Mediate SurvivalIn VitroandIn Vivoduring the Prolonged Oxidative Stress Response in Bacteroides fragilis

“…However, when the integrity of the intestinal wall is breached due to trauma, abdominal surgery, or diseases such as appendicitis, perforated ulcer, diverticulitis, and colon cancer, translocation of the normal flora into the peritoneal cavity can result in peritonitis and establishment of an intra-abdominal abscess. The inability of the host immune system to resolve the abscess can lead to bacteremia, sepsis, and in certain instances death (5,6). B. fragilis is the most common anaerobe isolated from intra-abdominal abscesses, and it has been demonstrated to possess many factors that promote its survival outside the intestinal tract, such as capsular polysaccharides, proteases, neuraminidase, iron acquisition, hemolysins, and resistance to oxidative stress (1,2,7,8).…”

Portal Cytokine Response and Metabolic Markers in the Early Stages of Abdominal Sepsis in Pigs

“…Pro-inflammatory cytokines are immediately generated by mesothelial cells and resident macrophages [1]. Intra-abdominal levels of pro-inflammatory cytokines in bacterial peritonitis have been shown to exceed by far the systemic levels, and this phenomenon has been explained by the concept of compartmentalisation, meaning that the peritoneal and the systemic inflammatory response occur in two functionally separate compartments [4,5].…”

“…The initial peritoneal response includes activation of resident macrophages and mesothelial cells, resulting in phagocytosis and recruitment of polymorphonuclear granulocytes and monocytes into the peritoneal cavity by chemotaxis [1]. The systemic dissemination may be mediated by microbial products or inflammatory mediators transported to the systemic circulation by the venous system or lymphatic drainage [2].…”

MiRNA-21 has anti-inflammatory effects in the macrophage response to peritonitis.

“…2) The early innate hours) which deals with the recognition of microbial-associated molecular patterns and in the inflammation, recruitment and activation of effector cells; and 3) the adaptive (>96 hours) which consists of recognition by B and T cells and clonal expansion and differentiation into effector cells 18,19 . All these process act synergistically to remove the infectious agent.…”

“…The human peritoneal resident leucocyte population comprises 45-90% macrophages, 10-47% lymphocytes and the rest NK cells, dendritic cells and neutrophils 26 . The mesothelial lining and macrophages are the main source of chemokines and cytokines that attract neutrophils and circulating monocytes to the peritoneum 18 . Cytokines bind to cell surface receptors on target cells, inducing intracellular signaling cascades to induce, or inhibit cytokine-regulated genes in the nucleus, thus manipulating cell activity.…”