Related Experiment Video
Updated: Aug 25, 2026
Lipopolysaccharide Infusion as a Porcine Endotoxemic Shock Model
Published on: December 8, 2023
Chronic morphine accelerates the progression of lipopolysaccharide-induced sepsis to septic shock
Frank M Ocasio1, Yuhui Jiang, Steven D House
1Department of Biology, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA.
Abstract:
Opiate addicts have been shown to have a high susceptibility to bacterial infection. We investigated how treatment with morphine alters lipopolysaccharide (LPS)-induced inflammatory responses in the rat. Chronic morphine alone elevated serum endotoxin levels. Animals treated with morphine and LPS (250 microg/kg) developed hypothermia, decreased mean arterial pressure (MAP), increased plasma thrombin anti-thrombin III (TAT) complex, and approximately 67% of animals exhibited progressive intramicrovascular coagulation. Morphine also enhanced LPS-induced leukocyte-endothelial adhesion (LEA), suppressed leukocyte flux, and corticosterone production, and elevated interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6 serum levels. Our study presents both the molecular and cellular mechanisms underlying the potentiated LPS-induced inflammation and accelerated progression to septic shock seen with chronic morphine exposure.
Insights
Chronic morphine use exacerbates inflammation and accelerates septic shock progression in rats by altering immune responses to lipopolysaccharide (LPS). This study reveals key molecular and cellular mechanisms behind this heightened susceptibility.
Area of Science:
- Immunology
- Pharmacology
- Pathophysiology
Background:
- Opiate addiction is linked to increased susceptibility to bacterial infections.
- Morphine's impact on inflammatory responses, particularly in the context of endotoxemia, requires detailed investigation.
Purpose of the Study:
- To investigate the effects of chronic morphine treatment on lipopolysaccharide (LPS)-induced inflammatory responses in a rat model.
- To elucidate the molecular and cellular mechanisms underlying morphine's potentiation of LPS-induced inflammation and septic shock progression.
Main Methods:
- Rats were treated with chronic morphine and/or LPS (250 microg/kg).
- Measurements included serum endotoxin levels, body temperature, mean arterial pressure (MAP), plasma thrombin anti-thrombin III (TAT) complex, leukocyte-endothelial adhesion (LEA), leukocyte flux, corticosterone, and inflammatory cytokine levels (IL-1beta, TNF-alpha, IL-6).
Main Results:
- Chronic morphine elevated serum endotoxin levels.
- Morphine-LPS co-treatment resulted in hypothermia, decreased MAP, increased TAT complex, and widespread intravascular coagulation (67% of animals).
- Morphine enhanced LPS-induced LEA, suppressed leukocyte flux and corticosterone, and elevated IL-1beta, TNF-alpha, and IL-6.
Conclusions:
- Chronic morphine exposure potentiates LPS-induced inflammation and accelerates the progression to septic shock.
- Morphine alters key immune cell functions and inflammatory mediator release, contributing to severe sepsis outcomes.
- Findings highlight the complex interplay between opiate use and immune system vulnerability during infection.
