Figure 2
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).