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High-dose interleukin 2 promotes bacterial translocation from the gut
J V Reynolds1, P Murchan, N Leonard
1Department of Surgery, St. James University Hospital, Leeds, UK.
British Journal of Cancer
|September 1, 1995
Summary
High-dose recombinant interleukin 2 (rIL-2) therapy can cause toxicity by promoting the translocation of gut bacteria. This study in rats suggests a potential mechanism for rIL-2-induced sepsis-like symptoms.
Area of Science:
- Immunology
- Gastroenterology
- Pharmacology
Background:
- High-dose recombinant interleukin 2 (rIL-2) therapy is associated with toxicity mimicking sepsis.
- The precise mechanism driving this toxicity remains incompletely understood.
- Bacterial translocation from the gut is a potential contributor to sepsis syndromes.
Purpose of the Study:
- To investigate the hypothesis that gut-origin bacteria translocation is involved in high-dose rIL-2 toxicity.
- To assess the dose-dependent effect of rIL-2 on bacterial translocation and intestinal morphology.
Main Methods:
- Male rats received varying doses of rIL-2 or saline intraperitoneally for 5 days.
- Ileal histomorphology was evaluated.
- Mesenteric lymph nodes were cultured for bacterial translocation.
Main Results:
- Escherichia coli translocation to mesenteric lymph nodes occurred in a dose-dependent manner with rIL-2 administration.
- All rats receiving the highest rIL-2 dose (10^5 IU) showed bacterial translocation.
- Intestinal changes, including increased submucosal lymphatics and mucosal disruption, were observed only at the highest rIL-2 dose.
Conclusions:
- Recombinant interleukin 2 promotes bacterial translocation from the gut in a dose-dependent manner.
- Bacterial translocation may be a key mechanism underlying the toxicity observed with high-dose rIL-2 therapy.
- These findings suggest a potential therapeutic target for mitigating rIL-2 toxicity.