The modulation of tumour necrosis factor-alpha, interleukin-1 alpha and glucose levels with GMDP and other analogues of muramyl dipeptide.
Immunomodulatory agent muramyl dipeptide (MDP) and seven of its analogues were tested for ability to counteract the toxic actions of lipopolysaccharide (LPS) in experimental mouse models. Female BALB/c mice were presensitized with Corynebacterium parvum (P. acnes) and given MDP or equimolar doses of one of its analogues after 2 weeks, followed by intravenous challenge with LPS 18 h later. This treatment produced a sharp increase in blood cytokine (TNF-alpha, IL-1 alpha) levels 4 h after LPS administration followed by a decline to control values after 6 h. Four analogues, GMDP, threonylMDP, GMDPBenz and GMDPOBut, were able to reduce the level of cytokines induced with LPS. For most of the analogues, the higher doses reduced the levels of TNF-alpha but slightly increased the concomitant IL-1 alpha levels. GMDP was the most effective compound tested in terms of reduction of TNF-alpha and IL-1 alpha levels, as well as for reduction of the hypoglycaemia caused by the administration of LPS.
Adeleye
T A
TA
MRC Tuberculosis and Related Infections Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Moreno
C
C
Ivanyi
J
J
Aston
R
R
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011425:Propionibacterium acnes / Q000276:immunology; D012477:Salmonella enteritidis; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D001786:Blood Glucose; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine