Anti-Inflammatory Properties of NAP in Acute Toxoplasma Gondii-Induced Ileitis in Mice.
The octapeptide NAP has been shown to exert neuroprotective properties. Here, we investigated potential anti-inflammatory effects of NAP in an acute ileitis model. To address this, C57BL/6j mice were perorally infected with Toxoplasma gondii (day 0). Within 1 week postinfection (p.i.), placebo (PLC)-treated mice developed acute ileitis due to Th1-type immune responses. Mice that were subjected to intraperitoneal NAP treatment from day 1 until day 6 p.i., however, developed less distinct macroscopic and microscopic disease as indicated by less body weight loss, less distinct histopathological ileal changes, and lower ileal apoptotic, but higher proliferating cell numbers, less abundance of neutrophils, macrophages, monocytes, and T lymphocytes, but higher numbers of regulatory T cells in the ileal mucosa and lamina propria, and lower concentrations of pro-inflammatory mediators in the ilea as compared to PLC controls at day 7 p.i. Remarkably, NAP-mediated anti-inflammatory effects could also be observed in extra-intestinal compartments including liver and spleen. Strikingly, lower MCP-1, TNF, and IL-12p70 serum concentrations in NAP as compared to PLC-treated mice at day 7 p.i. indicate a pronounced systemic anti-inflammatory effect of NAP in acute ileitis. These findings provide first evidence for NAP as a potential novel treatment option in intestinal inflammation.
Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
Markus M
MM
Heimesaat
Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
André
A
Fischer
Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology/Research Center ImmunoSciences (RCIS), Charité - University Medicine Berlin , Berlin, Germany.
Anja A
AA
Kühl
Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
Ulf B
UB
Göbel
Department of Clinical Biochemistry, Sackler School of Medicine, Aviv University , Aviv, Israel.
Illana
I
Gozes
Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
Stefan
S
Bereswill
ADNP; NAP; Th1-type immunopathology; Toxoplasma gondii; acute ileitis; anti-inflammatory effects; gut–brain axis; immunomodulatory properties