Differential role of interferon-gamma in the potentiating effect of muramyl peptides for enhanced responses to lipopolysaccharide in mice: effect of cyclosporin A.
Cyclosporin A (CsA) administration reduced mortality in mice sensitized to endotoxic toxicity by various agents, such as muramyl dipeptide (MDP) or a lipophilic derivative. CsA is an inhibitor of a variety of T cell responses, suggesting that muramyl peptides could influence LPS-induced effects via the release of lymphokine. The potentiation of TNF production by pretreatment with muramyl peptides was comparable in nude mice and in controls, indicating that it is a T-independent mechanism, and CsA produced a similar inhibition in both groups. Neutralizing antibody to IFN-gamma did not change the elevated TNF level obtained in the blood when LPS was given after a muramyl peptide. However, the same treatment with anti-IFN-gamma MAb prevented the death of mice challenged with LPS plus MDP or plus a lipophilic derivative displaying similar effects. In comparing three selected muramyl peptides, we also show that the priming effect could be dissociated from the toxic synergism with LPS.
Beigneux
A
A
Laboratory of Immunopharmacology, CNRS, Paris, France.
Huang
J
J
Le Contel
C
C
Heremans
H
H
Parant
M A
MA
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D016572:Cyclosporine / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D007371:Interferon-gamma / Q000276:immunology / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D008969:Molecular Sequence Data; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma; D016572:Cyclosporine