Tang W W, Feng L, Mathison J C, Wilson C B
Department of Immunology, Scripps Research Institute, La Jolla, California.
Lab Invest. 1994 May;70(5):631-8.
Cytokines are intercellular polypeptide messengers that mediate immune and inflammatory responses. The temporal profile of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha (TNF-alpha), and monocyte chemotactic protein 1 (MCP-1) expression was examined in anti-tubular basement membrane (TBM) antibody-associated tubulointerstitial nephritis (TIN).
TIN was induced by immunization of Brown Norway rats with bovine cortical TBM, whereas control rats received ovalbumin. Whole kidney RNA was assessed with the RNase protection assay 3, 7, 8, 9, 10, 12, and 14 days after immunization. Cytokine mRNA expression was correlated with TNF-alpha bioactivity, renal intercellular adhesion molecule-1 expression, and CD18-positive leukocyte infiltration by immunohistochemistry.
Increased IL-1 beta, TNF-alpha, and MCP-1 mRNA relative to glyceraldehyde-3-phosphate dehydrogenase appeared on day 7 when TIN involved 10 to 40% of the cortex, and peaked rapidly on day 8 when there was 60 to 80% cortical involvement (at which time 75 to 80% of the infiltrating cells were neutrophils). The increase in TNF-alpha mRNA correlated with increased bioactivity. The influx of mononuclear cells on day 8 was preceded by the expression of MCP-1 mRNA. The infiltrating leukocytes expressed the leukocyte beta 2-integrin (CD18) and were found in areas with increased intercellular adhesion molecule-1 expression. The mRNAs for IL-1 beta, TNF-alpha, and MCP-1 were undetectable by day 10 (at which time 95% of the infiltrating cells were mononuclear). An increase in IL-1 receptor antagonist mRNA paralleled those of IL-1 beta. The expression of IL-6 mRNA was similar to that for IL-1, except that it disappeared by day 9.
There is a temporal association in the expression of IL-1 beta, TNF alpha, MCP-1, and IL-6 with the upregulation of intercellular adhesion molecule-1 and leukocyte infiltration within the tubulointerstitium in anti-TBM antibody-associated TIN. The narrow window of time through which these cytokines are expressed and the coincidence of their peak expression on day 8 suggest complex cytokine interactions in the pathogenesis of anti-TBM antibody TIN.
细胞因子是介导免疫和炎症反应的细胞间多肽信使。在抗肾小管基底膜（TBM）抗体相关的肾小管间质性肾炎（TIN）中，检测了白细胞介素-1β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）和单核细胞趋化蛋白1（MCP-1）表达的时间特征。
通过用牛皮质TBM免疫棕色挪威大鼠诱导TIN，而对照大鼠接受卵清蛋白。在免疫后3、7、8、9、10、12和14天，用核糖核酸酶保护分析法评估全肾RNA。通过免疫组织化学将细胞因子mRNA表达与TNF-α生物活性、肾细胞间黏附分子-1表达以及CD18阳性白细胞浸润相关联。
相对于甘油醛-3-磷酸脱氢酶，IL-1β、TNF-α和MCP-1 mRNA在TIN累及皮质的10%至40%时于第7天出现增加，并在第8天皮质累及60%至80%时迅速达到峰值（此时75%至80%的浸润细胞为中性粒细胞）。TNF-α mRNA的增加与生物活性增加相关。在第8天单核细胞流入之前，MCP-1 mRNA表达增加。浸润的白细胞表达白细胞β2整合素（CD18），并在细胞间黏附分子-1表达增加的区域被发现。到第10天，IL-1β、TNF-α和MCP-1的mRNA无法检测到（此时95%的浸润细胞为单核细胞）。IL-1受体拮抗剂mRNA的增加与IL-1β的增加平行。IL-6 mRNA的表达与IL-1相似，只是在第9天消失。
在抗TBM抗体相关的TIN中，IL-1β、TNF-α、MCP-1和IL-6的表达与肾小管间质内细胞间黏附分子-1的上调和白细胞浸润存在时间关联。这些细胞因子表达的时间窗口狭窄以及它们在第8天的峰值表达一致，提示在抗TBM抗体TIN的发病机制中存在复杂的细胞因子相互作用。
