[Advances in the development of neutralizing therapies for sepsis].
Lipopolisaccharide (LPS), also called endotoxin, is the major component of the external membrane in Gram negative bacteria. This molecule is released to circulation by the bacteria, producing a large variety of toxic and pro-inflammatory effects which are associated with lipid A as well as with sepsis pathogenesis. Many physiological phenomena produced by LPS arise from this molecule's capacity to activate cells in the host immune system such as monocytes, macrophages and polymorphonuclear leukocytes. This process leads to a local inflammation, and it is beneficial for the host. However, if the amount of LPS released exceeds the critical concentration threshold an augmented release of inflammatory cytokines as TNF-alpha, and interleukines (IL) produce a severe sepsis. This fact led us to find therapeutical alternatives able to neutralize circulating endotoxin. This work is focused on the experimental results obtained in vivo and in vitro using synthetic proteins and peptides in order to neutralize LPS, and on future perpectives in this research area that offer the use of lipoprotein and in particular apolipoprotein A-I and mutants or peptides derived from this protein.
Florencia Henning
María
M
Instituto de Investigaciones Bioquímicas, Facultad de Ciencias Médicas, La Plata, Argentina.
Garda
Horacio
H
Bakás
Laura
L
D000890:Anti-Infective Agents / Q000627:therapeutic use; D016632:Apolipoprotein A-I / Q000378:metabolism; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007378:Interleukins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000502:physiology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000890:Anti-Infective Agents; D016632:Apolipoprotein A-I; D004731:Endotoxins; D007378:Interleukins; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D010455:Peptides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha