[Protection of PD-1 against LPS-induced endotoxemia and the underlying mechanism].

OBJECTIVE

Gram-negative bacteria-induced multiple organ failure/dysfunction syndrome (MOF/MODS) is one of the leading causes of death through the world. The member of immunoglobulin family programmed death-1 (PD-1) is a negative immune regulator. This study investigated the protective effect of PD-1 as well as the underlying mechanism in LPS-induced endotoxemia.

METHODS

Ten PD-1(+/+) and ten PD-1 knockout (PD-1(-/-)) mice were injected peritoneally with LPS (10 mg/kg), and the survival was observed within 72 hrs after LPS injection. The other 40 PD-1(+/+) and 40 PD-1(-/-) mice were injected peritoneally with LPS (5 mg/kg). Blood samples were collected before injection and 1.5, 3 and 6 hrs after LPS injection (n=10 each time point). Serum levels of various inflammatory mediators were measured using ELISA.

RESULTS

The survival rate in PD-1(-/-) mice was noticeably lower than that in PD-1(+/+) mice after 10 mg/kg LPS injection. Serum levels of inflammatory mediators TNF-α, IL-1β, IL-12 and IL-17 in PD-1/mice were higher than those in PD-1(+/+) mice after 5 mg/kg LPS injection.

CONCLUSIONS

PD-1 can protect mice from LPS-induced endotoxemia probably through its regulation on inflammatory mediator production.