Fig. 6 | npj Biofilms and Microbiomes

Fig. 6

From: New melanocortin-like peptide of E. coli can suppress inflammation via the mammalian melanocortin-1 receptor (MC1R): possible endocrine-like function for microbes of the gut

Fig. 6

MECO-1 rescues mice from lethal sepsis. a Endotoxin. Balb/C mice (males) were injected once intraperitoneally with LPS at a dose estimated to be an LD75. Immediately thereafter, the first doses of MECO-1 at 0.5 mg/kg (low dose), MECO-1 at 5 mg/kg (high dose), alpha-MSH at 5 mg/kg (high dose) or saline alone were administered intraperitoneally. Peptide or saline were given twice daily for 3 days for a total of six doses. Ten mice were in each group. Survival was monitored daily for 2 weeks. The survival benefits of MECO-1 and alpha-MSH were each statistically significant (**p < 0.01-log-rank test) vs. saline treated mice. b Cecal ligation and puncture. Balb/C mice were subjected to cecal ligation and puncture (CLP). Starting 24 h post-surgery, treatment was inaugurated, two doses daily for 3 days, for a total of six doses; MECO-1 at 0.5 mg/kg (low dose, n = 10) and MECO-1 at 5 mg/kg (high dose, n = 10) were compared to saline alone (n = 13) and alpha-MSH at 5 mg/kg (high dose, n = 10). Animals were monitored for survival for 14 days. The survival benefit of MECO-1 was statistically significant (high dose **p < 0.01 and low dose *p < 0.05 –log-rank test). In this study, one alpha-MSH animal died on the last day of the experiment, so that the benefit of alpha-MSH escaped significance (p = 0.08 changed from p < 0.05). Note that the high dose of MECO-1 is equal in mg/kg to the high dose alpha-MSH but is less than half on a molar basis. Low dose MECO-1 is ten-fold less than the high dose of MECO-1 and less than one 20th on a molar basis of the high dose of alpha-MSH. On face, our data with CLP (and with LPS) suggest the possibility that in protecting mice from death, MECO-1 may be (up to 30 times) more potent than alpha-MSH, whereas in vitro (see later) they appear to be equipotent. We tentatively propose that the basis for these differences are in the pharmacokinetics

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