Naito T, Yokoyama H, Moore K J, Dranoff G, Mulligan R C, Kelley V R
Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston 02115, USA.
Am J Physiol. 1996 Sep;271(3 Pt 2):F603-9. doi: 10.1152/ajprenal.1996.271.3.F603.
Conflicting reports claim that circulating interleukin (IL)-6 promotes or suppresses renal disease. Although autoimmune MRL-lpr mice have an increase in serum IL-6, and kidneys can produce IL-6, the relevance of systemic and local exposure remains undefined. To investigate the impact of IL-6 on kidney disease, we constructed a gene transfer approach to deliver sustained, stable IL-6 into the kidney and circulation. We infused syngeneic genetically modified tubular epithelial cells (IL-6-TEC) under the renal capsule of autoimmune and nonautoimmune mice. IL-6-TEC did not incite renal injury in any strain. Furthermore, serum IL-6 levels, which were increased three- to fivefold by IL-6-TEC, did not alter the contralateral kidney. Therefore, neither local nor systemic exposure to IL-6 promoted renal injury. As opposed to IL-6, we previously established that granulocyte macrophage (GM)-colony-stimulating factor (CSF) initiates renal injury in autoimmune mice. To determine whether IL-6 could suppress GM-CSF-incited damage, we infused GM-CSF-TEC TEC along with IL-6-TEC. Local production of IL-6 into the kidney did not alter the tempo or severity of GM-CSF-induced injury. Thus neither local nor systemic delivery of IL-6 promotes or suppresses kidney disease.
相互矛盾的报道称，循环中的白细胞介素（IL）-6可促进或抑制肾脏疾病。尽管自身免疫性MRL-lpr小鼠血清IL-6水平升高，且肾脏可产生IL-6，但全身暴露和局部暴露的相关性仍不明确。为了研究IL-6对肾脏疾病的影响，我们构建了一种基因转移方法，将持续、稳定的IL-6输送到肾脏和循环系统中。我们将同基因的转基因肾小管上皮细胞（IL-6-TEC）注入自身免疫性和非自身免疫性小鼠的肾包膜下。IL-6-TEC在任何品系中均未引发肾损伤。此外，IL-6-TEC使血清IL-6水平升高了三到五倍，但并未改变对侧肾脏。因此，局部或全身暴露于IL-6均未促进肾损伤。与IL-6相反，我们之前证实粒细胞巨噬细胞（GM）-集落刺激因子（CSF）可引发自身免疫性小鼠的肾损伤。为了确定IL-6是否能抑制GM-CSF引发的损伤，我们将GM-CSF-TEC与IL-6-TEC一起注入。肾脏局部产生IL-6并未改变GM-CSF诱导损伤的进程或严重程度。因此，局部或全身给予IL-6均不会促进或抑制肾脏疾病。
