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

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Abstract
To determine if exogenous interleukin (IL)-10 will decrease the morbidity or mortality of sepsis induced by cecal ligation and puncture. Prospective, randomized, controlled study. University research laboratory. Adult, female, Balb/c mice. 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. 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 [micro sign]g/mouse 2:12; 1 [micro sign]g/mouse 8:25; 0.1 [micro sign]g/mouse 1:12) or a 23-gauge needle (cecal ligation and puncture alone 13:29; IL-10 1 [micro sign]g 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 [micro sign]g/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 106, 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. Our data indicate that exogenous IL-10 fails to improve morbidity or mortality in the clinically relevant cecal ligation and puncture model of sepsis. (Crit Care Med 1998; 26:895-904)