Tim-3 In The Inflammatory Reaction After Acute Hypertensive Intracerebral Hemorrhage

Acute hypertensive intracerebral hemorrhage is a disease that seriously threat human health, the mortality of it is 40-60%, and the rate of handicap is 70-80% among the survival. Acute hypertensive ICH could induce stress reaction of different degree, and further affect the rehabilitation and prognosis of patients. Recently epidemiological studies and animal experiments have demonstrated that the inflammatory reaction after acute intracerebral hemorrhage is more serious than non-hemorrhagic injury. Microglia was activated after the intracerebral hemorrhage, and then induced the generation of chemotactic factor as well as the recruitment of peripheric immunocyte. The first step of these complex programs is the infiltration of leucocyte, release of inflammatory factor, and the accumulation of macrophages.Tim-3 is one member of T cell immunoglobulin domain and mucin domain protein (Tim) family; it can improve the number and activity of macrophages via activating Thl cells, and promote the Thl cells-induced immune response. Recent studies showed that besides Thl cells, CD8+T lymphocytes, dendritic cells and NK cells also express Tim3, which plays important role in regulating the function of these cells and is involved in the development of many kinds of inflammatory diseases. Till now, there is no report about the roles of Tim3 in the development of ICH. In the present study, we performed a preliminary study on the roles of Tim3 in the development of ICH, which might provide novel data for the mechanisms of ICH.Objectives:1. Clinical and serum data from 22 cases of acute hypertensive ICH patients were retrospectively studied. The relationship of blood glucose and leukocyte number with the degree of brain damange and prognosis was statistically analyzed.2. Tim3 expression level on peripheral T lymphocyte from ICH patients and healthy controls was detected. The difference between these two groups was statistically analyzed.3. The relationship of the ratio and Tim3 expression level of peripheral T lymphocytes with the degree of brain damange and prognosis was statistically analyzed.Methods:1. Twenty-two cases of acute hypertensive ICH patients who were treated by expectant treatment or surgical operation in our hospital from 2009 to 2010 were retrospectively studied. The relationship of blood glucose and leukocyte number with the degree of brain damange and prognosis was statistically analyzed by using Spearman. At the same time,32 cases of peripheral blood from healthy persons were collected as control groups.2. The alteration of Tim-3 protein expression CD3+T cells,CD4+T cells and CD8+T cells from 22 cases of acute hypertensive ICH and 32 cases of healthy controls was examined by flow cytometry.3. Statistical software Prism GraphPad was used for statistical treatment. T test was-used for interclass difference test. Spearman rank correlation analysis was used for correlation test.Results:1. The average blood glucose level of 22 cases of ICH patients was 8.5 mmol/l, among which those of 11 cases was higher than normal value. Moreover, the blood glucose level was significantly inversely correlated with GCS score. The average leukocyte number of 22 cases of ICH patients was 10.8×109/L, among which those of 9 cases was higher than normal value. Moreover, the leukocyte number was significantly inversely correlated with GCS and GOS score.2. There is no significant difference in the ratio of peripheral T lymphocyte between ICH patients and healthy control. The positive rate of Tim-3 on CD3+T cells from healthy control groups is 6.356±0.6162, which is significantly higher than that of patients with acute hypertensive ICH(3.321±0.5027, P=0.0185). The change pattern of Tim-3 positive rate on CD8+T cells was similar with that of CD3+T cells. Tim-3 positive rate on CD8+T cells from patients with acute hypertensive ICH was significantly downregulated from 23.96±2.631 to 11.67±2.630 (P=0.0041) Conversely, Tim3 positive rate on CD4+T cells from patients with acute hypertensive ICH was slightly upregulated from 4.525±0.5788 to 6.153±1.118 (P=0.1715)3. Tim3 expression level on T lymphocyte of ICH patients was correlated with the degree of brain damange and prognosis.4. Tim3 expression level on T lymphocyte of ICH patients had no correlation with the blood glucose level.Conclusions:1. There is close correlation between the degree of brain damange, prognosis and the blood glucose level, the leukocyte number, which indicates that both blood glucose and inflammatory response play important role in the development of ICH.2. The positive rate of Tim-3 on total CD3+T cells from patients with acute hypertensive ICH was significantly lower than that of healthy control groups. However, the change pattern of Tim-3 positive rate on CD8+ T cells and CD4+ T cells was different between each other. Tim-3 positive rate on CD8+ T cells from patients with acute hypertensive ICH was downregulated compared with healthy control groups, while it was upregulated on CD8+ T cells. Tim-3 might be involved in modulating the inflammaroty response in the brain by regulating its expression on CD8+ T cells and CD4+ T cells and might play important roles in the development of acute hyprertensive ICH.3. Detection of TIM-3 expression level on peripheral T cells of patients with acute hyprertensive ICH might be used as a clinical marker to predict inflammatory reaction after acute hypertensive ICH and new gene therapy target of acute ICH.