Inaba Y, Ishiguro A, Shimbo T
Department of Pediatrics, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan.
Pediatr Res. 1997 Dec;42(6):788-93. doi: 10.1203/00006450-199712000-00012.
Neutrophils in the cerebrospinal fluid (CSF) increase during the initial stage of meningitis. Some cytokines induce the accumulation of such neutrophils, and we and other investigators have revealed transient increases in the levels of granulocyte-colony stimulating factor (G-csf) and IL-8 in the CSF of patients with meningitis. To explore the coordination of other cytokines with G-csf and IL-8 in the neutrophil accumulation in the CSF, we herein investigated macrophage inflammatory protein-1alpha (MIP-1alpha), which can induce the infiltration of neutrophils. The modulation of MIP-1alpha levels in the CSF in children with bacterial (n = 10) and aseptic (n = 22) meningitis was examined using an ELISA. MIP-1alpha levels in the CSF were detectable at the stage with symptoms of meningitis: 289.9 +/- 270.7 ng/L in the bacterial meningitis group and 16.1 +/- 12.5 ng/L in the aseptic meningitis group. These levels decreased with the improvement of symptoms. MIP-1alpha was not detectable (<6 ng/L) in all of the control patients without meningitis (n = 19). The MIP-1alpha levels in the CSF showed a significant correlation with the CSF neutrophil counts (r = 0.750, p < 0.0001; n = 80) of meningitis, and the values of MIP-1alpha (log ng/L)/neutrophil counts (log/L) ratio were calculated (1.003 +/- 0.576). The MIP-1alpha levels in the serum were significantly lower than those in the CSF (p = 0.0464). We found MIP-1alpha mRNA in the CSF cells by the reverse transcriptase-PCR method, and high levels of MIP-1alpha protein in the culture media from mononuclear cells in the CSF in vitro. In summary, The MIP-1alpha level increases in the CSF at the symptomatic stage of meningitis in children, and its cellular source is, in part, mononuclear cells which have infiltrated the CSF. We propose that MIP-1alpha, in addition to G-csf and IL-8, plays an important role in the accumulation of neutrophils in the CSF of patients with meningitis.
在脑膜炎初期，脑脊液（CSF）中的中性粒细胞会增加。一些细胞因子会诱导此类中性粒细胞的聚集，我们和其他研究人员已发现脑膜炎患者脑脊液中粒细胞集落刺激因子（G-csf）和白细胞介素-8（IL-8）水平会短暂升高。为了探究其他细胞因子与G-csf和IL-8在脑脊液中性粒细胞聚集中的协同作用，我们在此研究了可诱导中性粒细胞浸润的巨噬细胞炎性蛋白-1α（MIP-1α）。我们使用酶联免疫吸附测定法（ELISA）检测了细菌性脑膜炎患儿（n = 10）和无菌性脑膜炎患儿（n = 22）脑脊液中MIP-1α水平的调节情况。在出现脑膜炎症状的阶段可检测到脑脊液中的MIP-1α水平：细菌性脑膜炎组为289.9±270.7 ng/L，无菌性脑膜炎组为16.1±12.5 ng/L。这些水平会随着症状的改善而降低。在所有无脑膜炎的对照患者（n = 19）中均未检测到MIP-1α（<6 ng/L）。脑脊液中的MIP-1α水平与脑膜炎患者脑脊液中的中性粒细胞计数显著相关（r = 0.750，p < 0.0001；n = 80），并计算了MIP-1α（log ng/L）/中性粒细胞计数（log/L）的比值（1.003±0.576）。血清中的MIP-1α水平显著低于脑脊液中的水平（p = 0.0464）。我们通过逆转录聚合酶链反应（RT-PCR）方法在脑脊液细胞中发现了MIP-1α信使核糖核酸（mRNA），并在体外脑脊液单核细胞的培养基中发现了高水平的MIP-1α蛋白。总之，在儿童脑膜炎的症状期，脑脊液中MIP-1α水平升高，其细胞来源部分是已浸润脑脊液的单核细胞。我们认为，除了G-csf和IL-8之外，MIP-1α在脑膜炎患者脑脊液中性粒细胞的聚集中也起着重要作用。
