[toggle_content title=”Abstract”]Intra-abdominal infection in patients following major visceral surgery is associated with high mortality. Using a macrophage depletion technique, we demonstrate that in murine septic peritonitis, Kupffer cells are a major source of systemic IL-10 levels. Kupffer cell-depleted mice were highly susceptible to the lethal effects of septic peritonitis and exhibited an increased bacterial load. Kupffer cell-depleted mice were protected by the administration of an IL-10-Fc fusion protein. Loss of Kupffer cell-derived IL-10 was associated with a weak increase in serum IL-12 levels, whereas TNF, IL-1, and IL-18 levels were not significantly elevated, suggesting that the loss of Kupffer cell-derived IL-10 did not result in a toxic cytokine release syndrome. Instead, loss of Kupffer cell-derived IL-10 was associated with a reduced splenocyte production of IFN- that is required for immune protection in murine septic peritonitis. Therefore, the results suggest that the protective function of IL-10 in septic peritonitis may not be restricted to the anti-inflammatory activities of IL-10. [/toggle_content]
[toggle_content title=”Clodronate Liposome Parameters”]
[custom_table]
| Clodronate Concentration |
Total Lipid Concentration |
Lipid Composition |
Lipid Mole % |
Liposome Type |
Control Liposomes |
| 5 mg/ml |
23.4 mg/ml |
EPC/Chol |
84/16 |
MLV |
none |
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[toggle_content title=”Animals and Dosing”]
[custom_table]
| Animal Description |
Clodronate Dose |
Dosing Method/Site |
Target Phagocytes |
Local Dosing? |
Local Results |
| C57BL/6, female mice, 8-12 w |
40 µl (diluted to 160 µl) |
i.v./not specified |
F4/80+ Kupffer cells |
no |
N/A |
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[toggle_content title=”Notes”]
- Liposome prep method cited was a review, so standard clodronate liposome parameters assumed.
- Animals were dosed with clodronate liposomes 24 h prior to surgical procedure used to induce (peritonitis) sepsis.
- Some groups were splenectomized to determine the contribution of splenic macrophages.
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[toggle_content title=”Results”]
- Peritoneal and aveolar macrophages were not reduced in number, but this was a 5X lower dose than often used in other papers (40 µl vs 200 µl).
- Authors report “complete” depletion of Kupffer cells along with splenic marginal macrophages and metallophilic macrophages, but not red pulp macrophages within 24 h by histology.
- Depletion lasted for at least 72 h.
- All other measurements on clodronate liposome-treated animals were either cytokine levels or IL-10 mRNA levels.
- The authors did not evaluate depletion in septic mice, therefore within the 12 h post-induction of sepsis (36 h post-clodronate liposome injection) before organs were harvested, would some migration of repopulating monocytes into tissues (including liver and spleen) occur?
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