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PRECLINICAL PUBLICATION · 2012

Prevention and mitigation of acute radiation syndrome in mice by synthetic lipopeptide agonists of Toll-like receptor 2 (TLR2).

Mouse / Radiation

Evidence by therapy association

Study details and outcomes are extracted in the context of a specific intervention. Separate associations are retained rather than silently merged.

PMID 22479357 ↗2012Reported benefit

Prevention and mitigation of acute radiation syndrome in mice by synthetic lipopeptide agonists of Toll-like receptor 2 (TLR2).

MouseRadiationICR (CD-1) primary model; BALB/cJ, C57BL/6J, B6.SJL-Ptprc Pepc/BoyJ and TLR2-knockout on C57BL/6 backgroundFemale for the main survival and cytokine studies; both sexes in the Neupogen comparison (15 male and 15 female per group) and chimera cytokine workn = n=15 per group for survival; n=6 per timepoint for cytokine…Subcutaneous throughout; intraperitoneal in the BALB/c bone marrow and spleen cellularity experiment4, 12, 40, 120, 400 and 1200 microg/kg in the prophylactic…Prophylaxis 0.5 to 72 h before irradiation, 24 h optimal; mitigation 10 min to…

Model: Bilateral total body gamma irradiation with caesium-137. High dose rate 2.3 Gy/min or 1.55 Gy/min, doses 4 Gy sub-lethal and 7 to 13 Gy for survival curves, 10 Gy LD100 in ICR and 9 Gy LD100 in C57BL/6J; low dose rate arm 0.41 plus or minus 0.05 cGy/min for 60 or 70 h giving 14.4 or 16.8 Gy; chimera conditioning 2 x 6 Gy 24 h apart

A single subcutaneous dose of synthetic lipopeptide given between 48 h before and 24 h after total body irradiation increased 30-day survival, raising LD50 from 8.5 to 11.25 Gy with a dose reduction factor of 1.32 for prophylaxis and 1.09 for mitigation. Protection required TLR2 and was largely ini…

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