AIM

To investigate the effects of growth hormone (GH) on NF-kappaB activity in neutrophils and neutrophils-mediated organ injury induced by lipopolysaccharide (LPS) in rats.

METHODS

Male Wistar rats challenged with or without LPS (5 mg/kg) were treated with varied doses of GH (0.5, 1.0, and 2.0 mg/kg) for 2 or 4 h. NF-kappaB activities in circulating neutrophils were measured with electrophoretic mobility shift assays (EMSA), and I-kappaB levels in circulating neutrophils were detected by Western blot. Lung neutrophils sequestration and lung microvascular permeability were measured at 4 h after LPS challenge.

RESULTS

Circulating neutrophils in LPS challenged rats had increased NF-kappaB activity and decreased I-kappaB level as compared with controls. GH dramatically increased NF-kappaB activity and I-kappaB degradation induced by LPS challenge in neutrophils. Also, subsequently, GH treatment increased lung neutrophils sequestration and lung microvascular injury induced by LPS.

CONCLUSION

These results suggest that treatment of GH is harmful, instead of beneficial, to LPS-induced organ injury. Increased neutrophils' NF-kappaB activity and lung neutrophils sequestration are critical in vivo mechanisms mediating GH action on LPS-induced organ injury.