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Monophosphoryl lipid A protects against gram-positive sepsis and tumor necrosis factor
M E Astiz1, A Galera, D C Saha
1St. Vincent's Hospital and Medical Center of New York, New York City 10011, USA.
Abstract:
Monophosphoryl lipid A (MPL) is a less toxic derivative of lipid A that enhances survival from endotoxemia. This study examined whether MPL induced resistance to Gram-positive sepsis and cytokines. Mice were administered MPL or saline (phosphate-buffered saline) and challenged 24 h later with live Staphylococcus aureus (SA), staphylococcus enterotoxin B (SEB), toxic shock syndrome toxin (TSST-1), and tumor necrosis factor (TNF). Survival was determined at 72 h. A separate set of animals was phlebotomized for determination of cytokines. MPL increased survival from S. aureus bacteremia from 20 to 87% (p < .05). Interleukin-6 (IL-6) and interleukin-1 (IL-1) and TNF were also significantly decreased. SEB and TSST survival were enhanced from 10 to 90% (p < .05). In SEB-treated animals, TNF and IL-6 levels were significantly decreased. Survival from TNF infusion was increased from 20 to 100% with MPL, however, no significant differences in cytokines were observed. These data suggest that MPL induces resistance to Gram-positive sepsis and cytokine-mediated activity.
Insights
Monophosphoryl lipid A (MPL) enhances survival against Gram-positive sepsis and reduces harmful cytokine activity. This study shows MPL significantly improves outcomes in models of Staphylococcus aureus bacteremia and toxic shock syndrome.
Area of Science:
- Immunology
- Microbiology
- Toxicology
Background:
- Monophosphoryl lipid A (MPL) is a detoxified derivative of lipid A.
- Lipid A is known to enhance survival in endotoxemia.
- The efficacy of MPL against Gram-positive sepsis and cytokine activity requires further investigation.
Purpose of the Study:
- To investigate the potential of MPL to confer resistance against Gram-positive bacterial infections.
- To determine if MPL can modulate cytokine responses in sepsis models.
- To evaluate MPL's protective effects against specific Gram-positive toxins and inflammatory mediators.
Main Methods:
- Mice were administered MPL or saline.
- Animals were challenged with Staphylococcus aureus (SA), staphylococcal enterotoxin B (SEB), toxic shock syndrome toxin (TSST-1), or tumor necrosis factor (TNF).
- Survival rates were assessed at 72 hours, and cytokine levels (IL-6, IL-1, TNF) were measured in a subset of animals.
Main Results:
- MPL administration significantly increased survival from S. aureus bacteremia (20% to 87%) and reduced IL-6, IL-1, and TNF levels.
- Survival rates from SEB and TSST-1 challenges were markedly enhanced (10% to 90%) with MPL treatment, accompanied by decreased TNF and IL-6.
- MPL improved survival from TNF infusion (20% to 100%), although cytokine levels did not differ significantly.
Conclusions:
- MPL demonstrates significant protective effects against Gram-positive sepsis models.
- MPL treatment effectively reduces pro-inflammatory cytokine production in response to certain Gram-positive bacterial challenges.
- These findings suggest MPL's potential as a therapeutic agent for Gram-positive sepsis and associated cytokine-mediated pathology.