[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.
Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China.
Li-Fen
LF
Yang
Fang
F
He
Jian
J
Zhang
Fei
F
Yin
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D019446:Endotoxemia / Q000517:prevention & control*; D005260:Female; D018664:Interleukin-12 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D061026:Programmed Cell Death 1 Receptor; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D020381:Interleukin-17; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12