Exogenous interleukin-10 fails to decrease the mortality or morbidity of sepsis

Crit Care Med. 1998 May;26(5):895-904. doi: 10.1097/00003246-199805000-00025.


Objective: To determine if exogenous interleukin (IL)-10 will decrease the morbidity or mortality of sepsis induced by cecal ligation and puncture.

Design: Prospective, randomized, controlled study.

Setting: University research laboratory.

Subjects: Adult, female, Balb¿c mice.

Interventions: Balb¿c mice were subjected to cecal ligation and puncture with an 18- or 23-gauge needle and treated with triple antibiotics. Mice were injected subcutaneously with recombinant human IL-10 (diluted in normal saline with 0.1% mouse serum albumin) and followed until death. In a separate experiment, IL-10 was also injected subcutaneously and lipopolysaccharide (LPS) injected intraperitoneally and plasma tumor necrosis factor concentrations measured 90 mins later.

Measurements and main results: In the LPS experiments, IL-10 decreased tumor necrosis factor (TNF) production by nearly 90%. For the cecal ligation and puncture experiments, temperature and movement were recorded continuously via implanted transmitters. Studies on mortality indicated that exogenous IL-10 given at 0, +6 and +12 hrs after surgery failed to increase survival when using an 18-gauge needle (alive:total cecal ligation and puncture alone 4:21; IL-10 10 microg/mouse 2:12; 1 microg/mouse 8:25; 0.1 microg/mouse 1:12) or a 23-gauge needle (cecal ligation and puncture alone 13:29; IL-10 1 microg 18:30). There was no difference in the number of hours to death between the groups. IL-10 did not prevent the hypothermia after cecal ligation and puncture or increase the animals' activity. To examine parameters of inflammation, mice were killed 8 hrs after 18-gauge cecal ligation and puncture. IL-10 (1 microg/mL) failed to reduce pulmonary neutrophil sequestration (lung myeloperoxidase, cecal ligation and puncture 107 +/- 10 [SEM], IL-10 107 +/- 5) or recruitment of neutrophils to the peritoneum (neutrophils x 10(6), cecal ligation and puncture 3.72 +/- 0.62; IL-10 3.49 +/- 0.37). IL-10 also failed to reduce the appearance of TNF or IL-6 in the plasma or peritoneal fluid. The chemokine KC was reduced in the peritoneal fluid but not the plasma and endogenous IL-10 production was not reduced in the peritoneum.

Conclusion: Our data indicate that exogenous IL-10 fails to improve morbidity or mortality in the clinically relevant cecal ligation and puncture model of sepsis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Injections, Intraperitoneal
  • Interleukin-10 / therapeutic use*
  • Ligation
  • Lipopolysaccharides / administration & dosage
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Sepsis / drug therapy*
  • Sepsis / etiology
  • Sepsis / pathology
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interleukin-10