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


METHODS
Prospective, randomized, controlled study.


METHODS
University research laboratory.


METHODS
Adult, female, Balb¿c mice.


METHODS
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.


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.


CONCLUSIONS
Our data indicate that exogenous IL-10 fails to improve morbidity or mortality in the clinically relevant cecal ligation and puncture model of sepsis.
Remick
D G
DG
Department of Pathology, University of Michigan, Ann Arbor 48109-0602, USA.
Garg
S J
SJ
Newcomb
D E
DE
Wollenberg
G
G
Huie
T K
TK
Bolgos
G L
GL
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000627:therapeutic use*; D008026:Ligation; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10