P351Prevention of t-cell specific immunosuppression after induced cerebral ischemia by the granulocyte-colony stimulating factor

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Cerebral ischemia is associated with immunosuppressive effects in peripheral blood, which lead to a higher susceptibility towards bacterial infections. G-CSF, which acts neuroprotective by multiple modes of action, is known to modulate inflammatory processes after induced stroke. To investigate its impact on T-cell specific immune response, we examined the effects of G-CSF in an experimental stroke model.


Stroke was induced in 70 male Wistar rats by occlusion of the middle cerebral artery, followed by reperfusion after 1 hour (tMCAO). G-CSF was applied once 30 minutes after induced tMCAO or daily for the next seven days and compared to an untreated tMCAO group. Silver staining was used to determine infarct size. Concentrations of T-lymphocytes in peripheral blood were measured before and 7 days after induced cerebral ischemia by flow cytometry. Apart from this cerebral translation levels of IL-10, as representative Th1- and IFN-y as Th2-specific cytokine, were determined using real-time PCR.


In both modes of treatment, G-CSF led to a reduction of the infarct size and an improved neurological outcome. Whereas a significant decrease in peripheral T-cells (CD3 + ) and T-helper cells (CD3 + CD4 + ) was detected in the infarct group without medical treatment, the application of G-CSF attenuated the reduction of T-lymphocytes depending on the mode of treatment. Thus the acute treatment application of G-CSF was associated with a lower amount of decrease, while the daily treatment gained to prevent the reduction in circulating


T-lymphocytes completely. Apart from that, the daily application of G-CSF was associated with an increase in IL-10 and a significant reduction of IFN-y in the infarcted brain hemisphere, indicating a shift from a balanced Th1/Th2 immune response towards an enhanced formation of Th2 cells.


Prevention of T-cell-specific immunosuppression constitutes an important activity of G-CSF, contributing to its beneficial properties in the course of cerebral ischemia. Based on the neuroprotective effects of a Th2-dominated immune response, lowering of Th1/Th2 ratio can additionally account for the reduction of infarct size.

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