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Effect of interleukin-10 on gut-derived sepsis caused by Pseudomonas aeruginosa in mice
T Matsumoto1, K Tateda, S Miyazaki
1Department of Microbiology, Toho University School of Medicine, Omori-Nishi, Ota-ku, Tokyo, Japan. tetsu@med.toho-u.ac.jp
Abstract:
We evaluated the protective effect of interleukin-10 (IL-10) against murine gut-derived sepsis caused by Pseudomonas aeruginosa. Gut-derived sepsis was induced by administering cyclophosphamide and ampicillin while feeding P. aeruginosa to specific-pathogen-free mice. Treating mice with recombinant human IL-10 (rhIL-10) at 1.0 or 5.0 microg/mouse twice a day following the second cyclophosphamide administration significantly increased the survival rate compared to that of control mice treated with saline; however, treatment with rhIL-10 at 0.1 microg/mouse did not result in significant protection. Bacterial counts in the liver, spleen, and blood were all significantly lower in mice treated with rhIL-10 than in saline-treated control mice. Treatment with rhIL-10 significantly suppressed tumor necrosis factor alpha, interleukin-1beta, interleukin-6, and gamma interferon levels in the serum of mice following induction of gut-derived sepsis. We also studied the effect of IL-10 on leukocyte recovery after cyclophosphamide treatment of mice. Administration of rhIL-10 intraperitoneally at 1. 0 microg/mouse significantly accelerated the recovery of leukocytes in comparison with that of the group of saline-treated controls. These results indicate that IL-10 shows a protective effect against gut-derived P. aeruginosa sepsis. We suspect that the mechanism of this effect is that IL-10 regulates in vivo production of inflammatory cytokines. Furthermore, acceleration of leukocyte recovery by IL-10 after cyclophosphamide-induced depression may also play an important role in this protection.
Insights
Interleukin-10 (IL-10) protects mice against Pseudomonas aeruginosa gut-derived sepsis. IL-10 treatment reduced bacterial load and suppressed inflammatory cytokines, improving survival rates.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Gut-derived sepsis is a severe condition often caused by opportunistic pathogens like Pseudomonas aeruginosa.
- Sepsis can lead to multi-organ failure and increased mortality.
- Interleukin-10 (IL-10) is a cytokine with known immunomodulatory functions.
Purpose of the Study:
- To evaluate the protective efficacy of recombinant human IL-10 (rhIL-10) against murine gut-derived sepsis induced by P. aeruginosa.
- To investigate the impact of IL-10 on bacterial load, inflammatory cytokine levels, and leukocyte recovery in a sepsis model.
Main Methods:
- Gut-derived sepsis was induced in specific-pathogen-free mice using cyclophosphamide, ampicillin, and P. aeruginosa.
- Mice were treated with varying doses of rhIL-10 or saline.
- Bacterial counts, serum cytokine levels (TNF-α, IL-1β, IL-6, IFN-γ), and leukocyte counts were measured.
Main Results:
- rhIL-10 treatment at 1.0 and 5.0 μg/mouse significantly increased survival rates compared to controls.
- Bacterial loads in the liver, spleen, and blood were significantly reduced in rhIL-10 treated mice.
- rhIL-10 suppressed serum levels of TNF-α, IL-1β, IL-6, and IFN-γ and accelerated leukocyte recovery post-cyclophosphamide.
Conclusions:
- IL-10 demonstrates a significant protective effect against P. aeruginosa-induced gut-derived sepsis in mice.
- The protective mechanism likely involves the regulation of pro-inflammatory cytokine production.
- IL-10's ability to accelerate leukocyte recovery may also contribute to its therapeutic benefit in sepsis.