Local and systemic innate immune response to secondary human peritonitis. Influence of micro-organism

Introduction: Our aim was to describe inflammatory cytokines response in the peritoneum and plasma of patients with peritonitis. We also tested the hypothesis that scenarios associated with worse outcome would result in different cytokine release patterns. Therefore, we compared cytokine responses according to the occurrence of septic shock, mortality, type of peritonitis and peritoneal microbiology. Methods: Peritoneal and plasma cytokines (interleukin (IL) 1, tumor necrosis factor a (TNFa), IL-6, IL-10, and interferon g (IFNg)) were measured in 66 patients with secondary peritonitis. Results: The concentration ratio between peritoneal fluid and plasma cytokines varied from 5 (2 to 21) (IFNg) to 1310 (145 to 3888) (IL-1). There was no correlation between plasma and peritoneal fluid concentration of any cytokine. In the plasma, TNFa, IL-6, IFNg and IL-10 were higher in patients with shock versus no shock and in nonsurvivors versus survivors (P ≤0.03). There was no differential plasma release for any cytokine between community-acquired and postoperative peritonitis. The presence of anaerobes or Enterococcus species in peritoneal fluid was associated with higher plasma TNFa: 50 (37 to 106) versus 38 (29 to 66) and 45 (36 to 87) versus 39 (27 to 67) pg/ml, respectively (P = 0.02). In the peritoneal compartment, occurrence of shock did not result in any difference in peritoneal cytokines. Peritoneal IL-10 was higher in patients who survived (1505 (450 to 3130) versus 102 (9 to 710) pg/ml; P = 0.04). The presence of anaerobes and Enterococcus species was associated with higher peritoneal IFNg: 2 (1 to 6) versus 10 (5 to 28) and 7 (2 to 39) versus 2 (1 to 6), P = 0.01 and 0.05, respectively). Conclusions: Peritonitis triggers an acute systemic and peritoneal innate immune response with a simultaneous release of pro and anti-inflammatory cytokines. Higher levels of all cytokines were observed in the plasma of patients with the most severe conditions (shock, non-survivors), but this difference was not reflected in their peritoneal fluid. There was always a large gradient in cytokine concentration between peritoneal and plasma compartments highlighting the importance of compartmentalization of innate immune response in peritonitis. Introduction Secondary peritonitis is a severe compartmentalized infectious insult characterized by a rapid response of innate immunity leading to a major inflammatory process. The initial response is usually followed by a postinjury depression of innate immunity in various types of sepsis [1-4]. However, there is a paucity of data regarding systemic and local innate immune responses during peritonitis in humans and on their relation to prognosis [5-8]. The outcome of secondary peritonitis has been shown to be influenced by several clinical and bacteriological features of the disease. We recently reported that two or more micro-organisms in peritoneal fluid culture, intra-peritoneal anaerobes, yeasts, or Enterococcus species were associated with worse prognosis. Other groups have suggested that postoperative peritonitis was also associated with worse outcome [9-11], a finding that our own observations did not corroborate [12]. Whether or not these features are associated with differential immune responses is unknown. Therefore, the aims of this study were: 1) to characterize the inflammatory mediator response (pro-inflammatory: IL-1, TNFa, IL-6, IFNg ; and anti-inflammatory: IL-10) in the peritoneal and blood compartments of patients with secondary * Correspondence: florence.riche@lrb.aphp.fr Departement d’Anesthésie-Réanimation, Hôpital Lariboisière, AP-HP, 2 rue Ambroise Paré, 75010 Paris, France Full list of author information is available at the end of the article Riché et al. Critical Care 2013, 17:R201 http://ccforum.com/content/17/5/R201 © 2013 Riché et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. peritonitis; 2) to evaluate the potential differences in mediator profiles between shocked and non-shocked patients, survivors and non survivors and according to the type of peritonitis (community-acquired or postoperative); and 3) to look at the potential impact of peritoneal microbiological findings on mediator release. Materials and methods Over a period of two years, all patients with secondary peritonitis admitted in our unit (surgical intensive care unit, Lariboisière University Hospital) were prospectively screened for peritoneal and plasma cytokine measurements. The study was approved by our Institutional Review Board (N° IRB00006477, Comité d’Ethique de la Recherche Biomédicale du GHU Nord). Plasma cytokine measurements were performed on leftovers of blood from routine daily samples and patients were informed during follow-up, but the need for written informed consent was waived. This cohort was a subgroup of a larger cohort of secondary peritonitis, which was previously reported [12]. Patients were included if they were older than 18 years and if the diagnosis of secondary generalized peritonitis (community-acquired and postoperative peritoneal infection) was confirmed surgically. They were not included if they had secondary peritonitis as a result of penetrating trauma, tertiary peritonitis defined as recurrent postoperative peritonitis, primary peritonitis (medical cause of intra-abdominal infection that did not require surgery) or if they received steroids as part of their treatment. Diagnosis and surgical management of generalized