Monophosphoryl lipid A protects against gram-positive sepsis and tumor necrosis factor.
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.
Astiz
M E
ME
St. Vincent's Hospital and Medical Center of New York, New York City 10011, USA.
Galera
A
A
Saha
D C
DC
Carpati
C
C
Rackow
E C
EC
D000818:Animals; D016470:Bacteremia / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D001427:Bacterial Toxins; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008050:Lipid A / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D012475:Salmonella; D013203:Staphylococcal Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D001427:Bacterial Toxins; D004768:Enterotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D008050:Lipid A; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal; C048436:monophosphoryl lipid A