gms | German Medical Science

Introduction: Local inflammatory response syndrome (LIRS) can be regarded as a reaction of tissue to impaired perfusion. It is characterized by infiltrating inflammatory cells and up-regulation of proteins mediating tissue response to overcome the consequences of injury. The particular role for activated macrophages is ill defined.

Materials and methods: We induced a LIRS via 30 min of ischemia in uni-nephrectomized rats, which were transgenic for the human FcgR1. 6 hours after reperfusion, the treatment group was injected with an immune toxin, targeted against the human FcgR1 and leading to apoptosis of activated macrophages. The control group received normal saline. After 24 hours of reperfusion the animals were sacrificed.

Results: Targeted treatment with the immune toxin resulted in less oxidative stress, a reduced renal injury and preserved renal function. Increases of circulating malondialdehyde (340±30 and 224±36 nmol/ml, respectively) and creatinine (69.17±5.81 and 54.67±7.63 µmol/l, respectively) were significantly less in the treatment group. The number of infiltrating macrophages (CD68) was significantly reduced (3.8±0.37 and 2.50±0.22 respectively), as was the expression of fibronectin (4±0.37 and 2.33±0.21, respectively).

Conclusion: The reduction of the number of activated macrophages after injury leads to a preserved organ function and texture in a rat model of ischemia-triggered LIRS. Our results demonstrate a valuable approach to treat tissue injury due to insufficient perfusion. Future investigations will have to characterize the effects of the immune toxin in greater detail for treating LIRS in the kidney as well as broaden its use to other affected organs.