Related Experiment Video
Updated: Mar 28, 2026
Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
Impact of the Timing of Morphine Administration on Lipopolysaccharide-Mediated Lethal Endotoxic Shock in Mice
Tomoko Fukada1, Hidehito Kato, Makoto Ozaki
1*Department of Anesthesiology, Tokyo Women's Medical University, School of Medicine †Department of Microbiology and Immunology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan.
Abstract:
Sepsis is a serious condition related to systemic inflammation, organ dysfunction, and organ failure. It is a subset of the cytokine storm caused by dysregulation of cytokine production. Morphine influences the severity of infection in vivo and in vitro because it regulates cytokine production. We investigated the immunological function of morphine using a mouse model of septic shock. We treated mice with α-galactosylceramide (2 μg/mouse) to induce lethal endotoxic shock following a challenge with lipopolysaccharide (LPS, 1.5 μg/mouse). This model represents acute lung injury and respiratory failure, and reflects the clinical features of severe septic shock. We evaluated the effect of the timing of morphine (0.8 mg/mouse) administration on the survival rate, cytokine production in vivo, and histological changes of mice with LPS-mediated lethal endotoxic shock. Morphine treatment before LPS challenge suppressed lethal endotoxic shock. In contrast, when we administered after LPS, morphine exacerbated lethal endotoxic shock; hematoxylin and eosin staining revealed a marked increase in the accumulation of infiltrates comprising polymorphonuclear leukocytes and mononuclear cells in the lung; and Elastica van Gieson staining revealed the destruction of alveoli. The plasma levels of tumor necrosis factor-α, interferon-γ, monocyte-chemotactic protein-1, and interleukin-12 in the group treated with morphine after LPS challenge were higher than those treated with morphine before LPS challenge. In conclusion, one of the factors that determine whether morphine exacerbates or inhibits infection is the timing of its administration. Morphine treatment before shock improved the survival rate, and morphine treatment after shock decreased the rate of survival.
Insights
Morphine
Area of Science:
- Immunology
- Pharmacology
- Pathophysiology
Background:
- Sepsis involves systemic inflammation and organ dysfunction, often linked to cytokine dysregulation.
- Morphine's impact on infection severity is known to be related to its effects on cytokine production.
- Understanding morphine's immunological role is crucial for managing sepsis-related complications.
Purpose of the Study:
- To investigate the immunological function of morphine in a mouse model of septic shock.
- To evaluate how the timing of morphine administration affects survival, cytokine levels, and lung histology in lipopolysaccharide (LPS)-induced endotoxic shock.
Main Methods:
- A mouse model of lethal endotoxic shock was induced using alpha-galactosylceramide and LPS.
- Morphine was administered either before or after LPS challenge.
- Survival rates, plasma cytokine levels (TNF-α, IFN-γ, MCP-1, IL-12), and lung tissue histology were assessed.
Main Results:
- Pre-treatment with morphine before LPS challenge suppressed lethal endotoxic shock and improved survival rates.
- Post-treatment with morphine after LPS challenge exacerbated shock, leading to increased lung inflammation, alveolar destruction, and higher levels of pro-inflammatory cytokines.
- Histological analysis showed increased leukocyte infiltration in the lungs of mice treated with morphine post-LPS.
Conclusions:
- The timing of morphine administration is a critical factor determining its effect on sepsis severity.
- Administering morphine before sepsis onset can be protective, while administration after sepsis onset can be detrimental.
- These findings highlight the complex immunomodulatory effects of morphine in the context of severe infection.
