Interleukin-18 concentration in the peritoneal fluid correlates with the severity of peritonitis

doi:10.1016/S0002-9610(03)00080-1

The American Journal of Surgery

Volume 185, Issue 6, June 2003, Pages 550-555

https://doi.org/10.1016/S0002-9610(03)00080-1 Get rights and content

Abstract

Background

Interleukin (IL)-18 is a novel cytokine that has recently been characterized as an inducer of interferon-gamma (IFN-γ). The aim of this study was to investigate the clinical significance of peritoneal IL-18 concentrations in patients with peritonitis.

Methods

We measured IL-18, IFN-γ, and IL-10 concentrations in the peritoneal fluid of 28 patients undergoing laparotomy for peritonitis. Correlations between the peritoneal cytokine concentrations and the severity of illness determined by systemic inflammatory response syndrome (SIRS) criteria, Acute Physiological and Chronic Health Evaluation II (APACHE II) score, peritoneal fluid bacterial culture results, subsequent development of organ failure, and length of hospital stay were assessed.

Results

Interleukin-18 concentration was significantly increased in patients who developed SIRS, in those with culture-positive peritonitis, and in those who developed organ failure, as compared with the other patients. Interleukin-10 concentration, which was also significantly increased in patients with culture-positive peritonitis, showed a close correlation with IL-18 concentration. Although a weak correlation was observed between IL-18 and IFN-γ concentrations, IFN-γ concentrations did not show any association with patients’ clinical parameters. However, the IFN-γ/IL-18 ratio was significantly lower in patients with an APACHE II ≥10, and in those with culture-positive peritonitis, as compared with the other patients.

Conclusions

Peritoneal IL-18 concentration increased in response to intraperitoneal bacterial infection and seemed to reflect the severity of peritonitis. However, the capacity of IL-18 to produce IFN-γ may be altered depending on the severity of peritonitis.

Section snippets

Patients and methods

Twenty-eight consecutive patients with peritonitis between 1998 and 2001 who required emergency laparotomy were enrolled in this study. The patients consisted of 18 men and 10 women, and their mean age was 63 years (range 16 to 88). Nine of 28 patients were diagnosed with upper digestive tract perforation, 9 with lower digestive tract perforation, 5 with strangulation bowel obstruction, 5 with bile peritonitis, and 1 with ovarian tumor perforation (Table1). All patients received systemic

Development of SIRS and peritoneal cytokine concentrations

A total of 14 of 28 patients met the SIRS criteria (Table 1). Interleukin-18 was detectable in all peritoneal fluid samples. The peritoneal IL-18 concentrations in patients who developed SIRS were significantly higher than in those who did not. However, there were no significant differences in the IFN-gamma or IL-10 concentrations between those who did and did not develop SIRS (Table 2).

APACHE II score and peritoneal cytokine concentrations

The mean APACHE II score of the patients was 9.6; it was 12.9 in patients who developed SIRS and 6.3 in

Comments

To our knowledge, the current study is the first to report peritoneal IL-18 concentrations in patients with peritonitis. One of the most important findings of this study was that intraperitoneal bacterial infection was associated with a significant increase in the peritoneal IL-18 concentration. This result confirms previous reports demonstrating that IL-18 plays a role in the host defense against infection. Sakao et al [24] reported that IL-18 knockout mice are more susceptible to lethal

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Citation Excerpt :
Serum IL-18 levels in nonseptic patients were not changed after surgery, but those levels in septic patients were significantly higher than those in healthy volunteers. We previously reported that the IL-18 concentrations in the peritoneal lavage fluid of septic patients as a result of peritonitis are extremely high and that these levels are correlated with the severity of the sepsis [16]. Emmanuilidis et al [17] reported that systemic IL-18 levels are increased significantly in septic patients compared with controls.
We investigated cellular immune responses, in particular interferon γ (IFN-γ) production, by peripheral blood mononuclear cells (PBMCs) in patients with septic and nonseptic surgical stress, focusing on interleukin (IL)-18 and its receptor (IL-18R).
Thirty-two patients with alimentary tract carcinoma who underwent elective surgery (OP) and 26 septic patients (SP) with peritonitis were enrolled in this study. Blood was collected on the first postoperative day (POD1), POD5, POD10, and POD15 in the OP group and on the emergency admission in the SP group. Ten healthy volunteers served as controls. PBMCs were cultured in the presence of anti-CD3 antibody or IL-2 and IL-12, with or without additional IL-18 stimulation, to measure IFN-γ production. IL-18R expression on CD56⁺NK (natural killer) cells was evaluated by flow cytometry.
IL-2– and IL-12–induced IFN-γ production by PBMCs was suppressed significantly in both the OP (POD5) and SP groups compared with that in healthy controls. Interestingly, additional IL-18 stimulation up-regulated IFN-γ production by PBMCs in the OP group as well as the control group, but not in the SP group. IL-18R expression on CD56⁺NK cells was maintained consistently in the OP group as well as the control group, but decreased in the SP group.
IFN-γ production induced by cytokines (IL-2 and IL-12) was suppressed in PBMCs from both patients with sepsis and those who had undergone elective surgery. However, IL-18R expression on CD56⁺NK cells was different between patients with sepsis and nonseptic surgical stress. Our results suggest that exogenous IL-18 administration may be effective in preventing immune suppression in patients with nonseptic elective surgery.
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Scientific paperInterleukin-18 concentration in the peritoneal fluid correlates with the severity of peritonitis

Abstract

Background

Methods

Results

Conclusions

Section snippets

Patients and methods

Development of SIRS and peritoneal cytokine concentrations

APACHE II score and peritoneal cytokine concentrations

Comments

J Surg Res

Adv Immunol

J Allergy Clin Immunol

Surgery

Surgery

Am J Surg

Prospective multicenter comparative study of the management of peritonitis. Quality assurance in severe intra-abdominal infection

Zentralbl Chir

Mediators of septic shocknew approaches for interrupting the endogenous inflammatory cascade

Crit Care Med

Perioperative TNF alpha and IL-6 concentrations correlate with septic state, organ function, and APACHE II scores in intra-abdominal infection

Eur J Surg

Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis

Br J Surg

Inflammatory cytokine response in patients with septic shock secondary to generalized peritonitis

Crit Care Med

Divergent efficacy of antibody to tumor necrosis factor-alpha in intravascular and peritonitis models of sepsis

J Infect Dis

High levels of tumor necrosis factor-alpha and interleukin-6 in the ascitic fluid of cirrhotic patients with spontaneous bacterial peritonitis

Clin Infect Dis

Spontaneous bacterial peritonitis is associated with high levels of interleukin-6 and its secondary mediators in ascitic fluid

Eur J Clin Invest

Interleukin-8 during peritonitis in patients treated with CAPDan in-vivo model of acute inflammation

Nephrol Dial Transplant

Plasma interleukin-6 levels in continuous ambulatory peritoneal dialysis and hemodialysis patients

Nephron

Clinical relevance of caspase-1 activated cytokines in acute pancreatitishigh correlation of serum interleukin-18 with pancreatic necrosis and systemic complications

Crit Care Med

Elevated interleukin (IL)-18 levels during acute graft-versus-host disease after allogeneic bone marrow transplantation

Br J Haematol

Scientific paper
Interleukin-18 concentration in the peritoneal fluid correlates with the severity of peritonitis