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Updated: May 21, 2026
Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
TRAIL administration down-modulated the acute systemic inflammatory response induced in a mouse model by
Annalisa Marcuzzi1, Paola Secchiero, Sergio Crovella
1Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
Abstract:
The potent inducer of apoptosis TRAIL/Apo2 ligand is now under considerations in clinical trials for the treatment of different types of cancer. Since the natural history of cancer is often characterized by microbial infections, we have investigated the effect of recombinant human TRAIL in a mouse model of systemic acute inflammation of microbial origin represented by BALB/c mice treated with either bacterial muramyldipeptide (MDP) or lipopolysaccharide (LPS). When administered intraperitoneally (i.p.), these inflammatory bacterial compounds triggered a severe systemic inflammatory response within 2h, represented by body temperature elevation, increase of circulating serum amyloid-A (SAA) and of the number of leukocytes in the peritoneal cavity. Moreover, both MDP and LPS induced a significant elevation of the circulating levels of several inflammatory cytokines and chemokines. Noteworthy, pre-treatment with recombinant human TRAIL 48 and 72 h before administration of either MDP or LPS, significantly counteracted all acute inflammatory responses, including the elevation of key pro-inflammatory cytokines/chemokines such as IL-1α, IL-6, G-CSF, MCP-1. These data demonstrate for the first time that TRAIL has a potent anti-inflammatory activity, which might be beneficial for the anti-tumoral activity of TRAIL.
Insights
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits potent anti-inflammatory effects. Pre-treatment with TRAIL significantly reduced systemic inflammation caused by bacterial compounds in mice.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2 ligand) is a key apoptosis inducer investigated for cancer therapy.
- Cancer progression is frequently associated with microbial infections and subsequent inflammation.
Purpose of the Study:
- To investigate the anti-inflammatory effects of recombinant human TRAIL in a mouse model of microbial-induced acute systemic inflammation.
- To determine if TRAIL can counteract inflammatory responses triggered by bacterial components like muramyldipeptide (MDP) and lipopolysaccharide (LPS).
Main Methods:
- BALB/c mice were treated with MDP or LPS to induce systemic inflammation.
- Recombinant human TRAIL was administered intraperitoneally 48 and 72 hours prior to inflammatory agent administration.
- Inflammatory markers including body temperature, serum amyloid-A (SAA), leukocyte count, and cytokine/chemokine levels (IL-1α, IL-6, G-CSF, MCP-1) were measured.
Main Results:
- MDP and LPS induced severe acute systemic inflammation, characterized by increased body temperature, SAA, and peritoneal leukocytes.
- Both bacterial compounds significantly elevated circulating inflammatory cytokines and chemokines.
- TRAIL pre-treatment markedly counteracted these inflammatory responses, including the reduction of key pro-inflammatory mediators.
Conclusions:
- TRAIL possesses significant potent anti-inflammatory activity.
- This anti-inflammatory property of TRAIL may enhance its therapeutic efficacy in cancer treatment, particularly in the context of microbial infections.
