Analysis of interleukin 6 and its soluble receptor in cerebrospinal fluid

在去年的报道中，我们提出胶质母细胞瘤细胞系T98G在感染疱疹病毒1型（HSV 1）时产生白细胞介素6（IL 6）。随后的实验表明，诱导IL 6产生的不是HSV感染本身，而是病毒制剂中污染的某种因子。低浓度脂多糖（LPS）对T98细胞产生IL 6无明显促进作用，但LPS刺激的外周血单个核细胞（PBM）培养上清具有较强的IL 6诱导活性。结果表明，低剂量LPS刺激的中性粒细胞（PMN）培养上清也具有同样的活性。此外，我们可以建议，在中性粒细胞的情况下，一些因子以外的IL-1可能发挥主要作用的IL-6诱导活性，而IL-1可能是重要的PBM的情况下。同样的结果，得到使用星形细胞瘤细胞系U373。最先出现在炎症部位的中性粒细胞参与调节IL 6的产生。研究了单纯疱疹病毒1型（HSV 1）感染前后U373细胞IL 6信使水平的变化，发现脑脊液中可溶性IL 6受体（sIL 6R）具有生物活性。因此，我们推测CSF中sIL 6R可能以IL 6-sIL 6R复合物的形式存在。令人惊讶的是，当将CSF应用于凝胶过滤并测定每个级分中的IL 6和sIL 6R时，没有观察到提示IL 6-sIL 6R复合物的峰。这可能表明只有一小部分sIL 6R与IL 6结合，其余sIL 6R和IL 6以游离形式存在。

In the report last year, we suggested that glioblastoma cell line T98G produce interleukin 6 (IL6) when it was infected with herpes virus type 1 (HSV1). Subsequent experiment revealed that it is not HSV infection itself but some factor contaminated in the virus preparation that induce IL6 production. Lipopolysaccharide (LPS) in low concentration dose not enhance IL6 production from T98G,but the supernatant of LPS stimulated peripheral blood mononuclear cells (PBM) culture has strong IL6 inducing activity. We could demonstrate that the supernatants of low dose LPS stimulated polymorphonuclear cell (PMN) also have the same activity. Furthermore, we could suggest that in case of PMN some factor other than IL1 may play major role for IL6 inducing activity, while IL1 may be important in case of PBM.The same results were obtained using astrocytoma cell line U373. It is interesting that PMN that may appear at inflammatory site at first are involved for the regulation of IL6 production. The change of IL6 message level in U373 cells with or without HSV1 infection is under investigation.The immunoreactive soluble IL6 receptor (sIL6R) present in cerebrospinal fluid is shown to biologically active. Thus, we speculated that sIL6R in CSF may be present in IL6-sIL6R complex. Surprisingly, when CSFs were applied to gel filtration and IL6 and sIL6R in each fraction were assayd, no peak suggesting IL6-sIL6R complex was observed. This may suggest that only a small part of sIL6R bind to IL6 and rest of sIL6R and IL6 is present in free form.