Figure 2From: An A2Aadenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models ATL313 protects mice in three different sepsis models. ATL313 protects mice from live E. coli challenge. Mice were injected with 1 × 108 CFU of live E. coli. Mice (N = 5 per group) were treated with PBS vehicle (white diamond), ATL313 (black circle), the antibiotic ceftriaxone (white triangle), or a combination of ceftriaxone and ATL313 (black square). Ceftriaxone was administered at a single dose of 25 mg/kg eight hours following inoculation. ATL313 (5 μg/kg) or PBS was dosed IP starting 8 hours after E. coli injection then every 6 hours spanning 48 hours. ATL313 + ceftriaxone treatment protects mice better than ceftriaxone treatment alone (* p = 0.013) and treatment with ATL313 alone prolongs life compared to E. coli untreated controls (#p = 0.031) (A). ATL313 protects mice from live S. aureus challenge. Mice were injected IP with 8 × 108 cfu of live S. aureus. Mice (N = 10–24 per group) were treated with PBS vehicle (white diamond), ATL313 (black circle), the antibiotic ceftriaxone (white triangle), or a combination of ceftriaxone and ATL313 (black square). Ceftriaxone was administered at a single dose of 25 mg/kg eight hours following inoculation. ATL313 (5 μg/kg) or vehicle was dosed IP starting at eight hours after S. aureus injection 4 times at 12 hour intervals. ATL313 + ceftriaxone treatment protects mice better than ceftriaxone treatment alone (* p = 0.02) and ATL313 treatment alone increases survival in S. aureus untreated controls (#p = 0.036) (B). ATL313 decreases LPS-induced mouse mortality via A2A AR-mediated mechanisms. Mice (N = 20–29 per group) were injected IP with LPS from E. coli (O111:B4, 5 mg/kg). One half hour prior to LPS challenge and at 6 hr intervals, PBS vehicle (white triangle) or ATL313 (black circle) was injected (5 μg/kg) IP for a total of 8 doses/48 hr. ATL313 protects the mice compared to LPS-challenged mice in the absence of ATL313 (* p = 0.005) (C).Back to article page