Modulating the functions of neutrophils and lipid peroxidation by FK506 in a rat model of thermal injury

Neutrophils diffusely invade lung, liver, kidney, intestine, muscle and burned skin following burn injury. To ameliorate this invasion and minimize its effects, neutrophils can be modulated by giving neutrophil inhibitors and modulators. In this study, FK506 was used to decrease neutrophil infiltration and lipid peroxidation in remote organs (lung, liver, kidney and intestine) in a burned rat model. FK506 is a new major immunosuppressive agent that is known to modulate neutrophils during inflammation. Neutrophil infiltration was assessed indirectly by measuring myeloperoxidase (MPO) activity biochemically in remote organs following 30% full thickness burn injury. Malondialdehyde (MDA), the end product of lipid peroxidation, was measured biochemically in remote organs and plasma to determine if there is a relationship between neutrophil infiltration and lipid peroxidation after burn injury. FK506 was given intramuscularly at the dose of 0.5 and 1.0 mg/kg for three days before burn injury. Thermal trauma to the skin caused a statistically significant increase in MPO activity and MDA content in remote organs. FK506 was effective in reducing lipid peroxidation and neutrophil infiltration especially at 24 h postinjury in lung, liver and kidney. FK506 may have some benefit (prophylactic) in reducing systemic neutrophilic injury and related lipid peroxidation in burns. (C) 1999 Elsevier Science Ltd and ISBI. All rights reserved.