Acute, fully reversible paw edema was produced in mice after systemic administration of muramyl dipeptide (MDP, i.e. N-acetylmuramyl-L-alanyl-D-isoglutamine). Its stereoisomer N-acetylmuramyl-D-alanyl-D-isoglutamine (MDP-D,D) was much less effective. The swelling of paws occurred very soon (1 h) after MDP injection, reached the maximum severity at an interval of 6 h and declined afterwards. While no substantial quantitative differences were found in the sensitivity of the various inbred strains of mice to edemagenic activity of MDP, athymic nude mice were completely resistant to the induction of edema. Formation of edema was blocked by silica, indomethacin (partially also by nordihydroguaiaretic acid), monoclonal antibodies against T-cells and their TH-subpopulation. It is suggested that the MDP-induced edema is a macrophage- and T-cell-dependent, prostaglandin- (and partially leukotriene)-mediated acute reaction associated with increased vascular permeability. Possible engagement of immune/inflammatory cytokines like IL-1 has been discussed. The data support the view that this type of edema is a consequence of changes in the activity of important cellular components of the immune system.

• MeSH
• acetylmuramyl-alanyl-isoglutamin toxicita   MeSH
• edém chemicky indukované   MeSH
• indomethacin farmakologie   MeSH
• kapilární permeabilita účinky léků   MeSH
• lékové interakce MeSH
• monoklonální protilátky imunologie   MeSH
• myši inbrední C57BL MeSH
• myši nahé MeSH
• myši MeSH
• oxid křemičitý farmakologie   MeSH
• stereoizomerie MeSH
• T-lymfocyty imunologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zadní končetina MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• indomethacin MeSH
• monoklonální protilátky MeSH
• oxid křemičitý MeSH

Immunomodulatory agents, muramyl dipeptide (MDP) and several of its analogues, i.e. adamantylamide dipeptide, murametide, murabutide and their glucosaminylated derivatives, were tested for edemagenic activity in rats. Given systemically in aqueous solutions, only MDP and glucosaminylated MDP, at the dose of 3 mg/kg (s.c. or p.o.), were found to produce edematous swelling of the paws. Local (intra-pad) application of MDP was more effective than the systemic one. Supernatants of macrophages, in vitro cultured in presence of MDP, caused the swelling as well. The edema was of a transient nature. After reaching the maximum severity (about 6 h after injection of MDP solution or 1 h after macrophage supernatants), it was subsiding and disappeared completely within approximately 6 days after cessation of the treatment. It was found that this type of rat paw edema is probably a prostaglandin-dependent consequence of macrophage activation. Hypotheses on the involvement of immunoregulatory cytokines, and possible chemical structure-inflammatory activity relationships have been suggested.

• MeSH
• acetylmuramyl-alanyl-isoglutamin * analogy a deriváty   chemie   farmakologie   MeSH
• adjuvancia imunologická farmakologie   MeSH
• edém chemicky indukované   patologie   MeSH
• inbrední kmeny potkanů MeSH
• indomethacin farmakologie   MeSH
• králíci MeSH
• krysa rodu Rattus MeSH
• makrofágy účinky léků   MeSH
• noha (od hlezna dolů) patologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zánět chemicky indukované   patologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin * MeSH
• adjuvancia imunologická MeSH
• indomethacin MeSH