IL-11 pretreatment reduces cell death after intestinal ischemia-reperfusion.

Abstract

BACKGROUND:

Intestinal ischemia-reperfusion (IR) injury results in enterocyte necrosis and apoptosis. This study was designed to evaluate the potential protective effects of interleukin-11 (IL-11) pretreatment on intestinal mucosa following IR injury.

MATERIALS AND METHODS:

Sham (n = 7) and control animals (n = 7) received 48 h of intravenous saline while treatment animals (n = 7) received IL-11 (750 microg/kg/day). Sham animals then underwent laparotomy alone, while control and treatment animals underwent 35 min of mesenteric artery occlusion and 120 min of reperfusion. Midjejunum samples were obtained and serum was drawn. Fluorometric assays were performed for hexosaminidase A (HEX A) and beta-glucuronidase (GLUC), markers of enterocyte necrosis. Apoptosis was quantified by TUNEL and confirmed by DNA fragmentation. Transcription of Bcl-2, an antiapoptotic regulator, was assessed by multiplex RT-PCR. Statistical analysis was performed using ANOVA and expressed as means +/- SEM.

RESULTS:

In pretreated animals, HEX A and GLUC activities after IR were reduced from 570 +/- 54 to 426 +/- 47 nmol/ml/h (P < 0.05) and from 183 +/- 29 to 125 +/- 7 nmol/ml/h (P < 0.01), respectively. Pretreated animals had a reduced number of apoptotic cells per 10 crypts (79 +/- 11) compared with untreated rats (255 +/- 17) after IR injury (P < 0.01). Mucosal DNA from pretreated rats qualitatively showed less fragmentation on electrophoresis. Relative Bcl-2 band intensity was higher in pretreated animals (1.04 +/- 0.09) compared with controls (0.78 +/- 0.07) (P < 0.05).

CONCLUSIONS:

IL-11 pretreatment reduced crypt cell apoptosis after IR injury, possibly by upregulating Bcl-2. Treated animals also demonstrated attenuation in the release of certain lysosomal enzymes. These data indicate that following IR injury, IL-11 improves enterocyte survival by reducing necrosis and apoptosis.

• Authors: Keith A Kuenzler, Philip Y Pearson, Marshall Z Schwartz
• Journal: The Journal of surgical research (J Surg Res) Vol. 108 Issue 2 Pg. 268-72 (Dec 2002) ISSN: 0022-4804 [Print] United States
• PMID: 12505051 (Publication Type: Journal Article)

Chemical References

• Enzymes
• Interleukin-11

Topics

• Animals
• Cell Death (drug effects)
• DNA Fragmentation
• Enzymes (blood)
• Immunohistochemistry
• In Situ Nick-End Labeling
• Interleukin-11 (pharmacology)
• Intestines (blood supply, pathology)
• Ischemia (genetics, pathology, physiopathology)
• Lysosomes (enzymology)
• Male
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (genetics, pathology, physiopathology)
• Reverse Transcriptase Polymerase Chain Reaction