Objective      To determine the anti-inflammatory effect of insulin-like growth factor 1 receptor (IGF-1R) selective inhibitor PQ401 in vitro and in vivo.       Methods      RAW264.7 cells were pre-incubated with 0.1

1 and 10 μmol/L PQ401 for 1 h and then stimulated with 10 μg/mL lipopolysaccharide (LPS) for 12 h. After RAW264.7 cells were treated with 10 μmol/L PQ401 for 1 h

followed by 10 μg/mL LPS stimulation for 6

12 and 24 h

the culture supernatants of the above cells were checked for the determination of tumor necrosis factor-α (TNF-α)

interleukin 1β (IL-1β) and interleukin 6 (IL-6) by enzyme linked immunosorbent assay (ELISA).  Fifty C57BL/6 mice were randomly divided into a control group

a model group and different dose PQ401 groups by 10 animals per  group. Intra-peritoneal injection of 10 mg/kg LPS  was given to the mice to establish the acute inflammatory model. The control group was  intra-peritoneally injected equal dimethyl sulfoxide. The PQ401 group were differently intra-peritoneally injected 10 mg/kg LPS and  25

50

100 mg/kg. All the mice were sacrificed in 12 h after injection. Blood samples were collected for the determination of TNF-α

IL-1β and IL-6  by ELISA

and for determination of alanine aminotransferase (ALT)

aspartate aminotransferase (AST) and total bilirubin (TBil) with an automatic biochemistry analyzer. Hepatic homogenate was also collected for detecting the expression of nuclear factor-κB p65 (NF-κB p65) by Western blotting.       Results      Compared with LPS alone

PQ401 resulted significant decreases of TNF-α

IL-1β and IL-6 in a dose- and time-dependent manner in the culture supernatants. In 12 h after modeling

the mice in the model group became lethargic and quiet

but PQ401 treatment was found to be able to greatly improve the general status of the mice. PQ401 could lower the serum levels of TNF-α

IL-1β and IL-6

and inhibit the liver levels of TNF-α

IL-1β and NF-κB p65.       Conclusion      PQ401 can inhibit the secretion of LPS-induced inflammatory cytokines in vitro and in vivo.