Tumor necrosis factor-α and interleukin-6 in cirrhotic patients with spontaneous bacterial peritonitis

Abstract

Aim: To evaluate the role of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis (SBP).

Methods: We prospectively studied 120 cirrhotic patients with SBP and 80 cirrhotic patients with sterile ascitic fluid. They included 144 males and 56 females with ages ranging between 34 and 62 years. The diagnosis of cirrhosis was established by clinical and laboratory criteria that did not require histological confirmation. The severity of underlying liver disease was evaluated using Pugh's modification of Child's criteria (Child-Pugh scores). Ascitic fluid was sent to the laboratory for cell count, culture, sensitivity testing, and measurement of chemical elements (i.e., albumin, glucose). Specimens were inoculated into aerobic and anaerobic blood culture bottles. Serum and ascitic fluid were also collected in sterile tubes at study entry (before the initiation of antibiotic treatment) and 48 h later. Assays for TNF-α and IL-6 in the serum and ascitic fluid were performed with an immunoenzymometric assay using manufacture's instructions.

Results: Cytokine levels in serum and ascitic fluid were significantly higher in the patients with SBP. (plasma TNF-α: 135.35 ng/mL ± 11.21 ng/mL vs 92.86 ng/mL ± 17.56 ng/mL, P < 0.001; plasma IL-6: 32.30 pg/mL ± 7.07 pg/mL vs 12.11 pg/mL ± 6.53 pg/mL, P < 0.001; ascitic fluid TNF-α: 647.54 ± 107.11 ng/mL vs 238.43 ng/mL ± 65.42 ng/mL, P < 0.001); ascitic fluid IL-6: 132.84 ng/mL ± 34.13 vs 40.41 ± 12.85 pg/mL, P < 0.001). About 48 (40%) cirrhotic patients with SBP developed renal and hepatic impairment and showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection. [(plasma TNF-α: 176.58 ± 17.84 vs 135.35 ± 11.21 ng/mL) (P < 0.001) and (IL-6: 57.83 ± 7.85 vs 32.30 ± 7.07 pg/mL) (P < 0.001); ascitic fluid TNF-α: 958.39 ± 135.72 vs 647.54 ± 107.11 ng/mL, (P < 0.001), ascitic fluid IL-6: 654.74 ± 97.43 vs 132.84 ± 34.13 pg/mL, (P < 0.001)]. Twenty nine patients (60.4%) with SBP and renal impairment died whereas, only four patients (5.55%) with SBP but without renal impairment died from gastrointestinal hemorrhage (P < 0.0005).

Conclusion: It appears that TNF-α production may enhance liver cell injury and lead to renal impairment. This correlated well with the poor prognosis and significantly increased mortality associated with SBP in cirrhotic patients.

Keywords: Cirrhosis; Interleukin-6; Spontaneous bacterial peritonitis; Tumor necrosis factor.

Figure 1

Comparison of groups Ia, Ib and II with regards to liver (A) and renal (B) function tests. Y-axis shows SI units of measurements.

Figure 2

Comparison of groups Ia, Ib and II with regards to serum tumor necrosis factor-α and interleukin-6 (A), ascitic fluid serum tumor necrosis factor-α and interleukin-6 (B) total cell count and ascitic fluid PNL (C). Y axis shows units of measurements for serum tumor necrosis factor-α (ng/mL); interleukin-6 (pg/mL) and white cell count (cmm³).

Figure 3

Comparison of patients in Child-Pugh class C with respect to serum tumor necrosis factor-α (A) and interleukin-6 (B) between Ia, Ib and II groups. Y axis shows units of measurements for serum tumor necrosis factor-α (ng/mL); IL-6 (pg/mL).

Figure 4

Comparison of patients in Child-Pugh class B with respect to serum tumor necrosis factor-α (A) and interleukin-6 (B) between Ib and II groups. Y axis shows units of measurements for serum tumor necrosis factor-α (ng/mL); interleukin-6 (pg/mL).