Analogues of muramyl dipeptide (MDP) and tuftsin limit infection and inflammation in murine model of sepsis.
Pharmacological manipulation of the balance between pro- and anti-inflammatory mediators emerges as a key aspect of a successful treatment of sepsis. A murine model of septic shock was developed and chosen conjugates (1a, 1b, 8a, 8c) and analogs (T2) of muramyl dipeptide and tuftsin were tested in this model as prospective anti-bacterial drugs or adjuvants. The phagocytic activity of monocytes/macrophages was determined (flow cytometry, bacterial clearance from vital organs). To evaluate cytokines levels (TNFalpha, IFNgamma, IL6, IL10) we used real-time PCR. The most promising immunomodulatory properties were displayed by the analogue T2 and two conjugates: 8a, 8c.
Wardowska
Anna
A
Laboratory of Clinical Immunology and Transplantology, Medical University of Gdansk, 1 Debinki Street, 80-210 Gdansk, Poland. anna.wardowska@amg.gda.pl
Dzierzbicka
Krystyna
K
Szaryńska
Magdalena
M
Dabrowska-Szponar
Maria
M
Wiśniewska
Katarzyna
K
Myśliwski
Andrzej
A
Trzonkowski
Piotr
P
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000627:therapeutic use*; D000818:Animals; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D004927:Escherichia coli Infections / Q000188:drug therapy; D020869:Gene Expression Profiling; D007155:Immunologic Factors / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D016133:Polymerase Chain Reaction / Q000379:methods; D018805:Sepsis / Q000188:drug therapy*; D014405:Tuftsin / Q000627:therapeutic use*
D016207:Cytokines; D007155:Immunologic Factors; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D014405:Tuftsin