A GENE-TRANSFER SYSTEM ESTABLISHES INTERLEUKIN-6 NEITHER PROMOTES NORSUPPRESSES RENAL INJURY

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 o f systemic and local exposure remains undefined. To investigate the im pact of IL-6 on kidney disease, we constructed a gene transfer approac h to deliver sustained, stable IL-6 into the kidney and circulation. W e infused syngeneic genetically modified tubular epithelial cells (IL- 6-TEC) under the renal capsule of autoimmune and nonautoimmune mice. I L-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 syste mic exposure to IL-6 promoted renal injury. As opposed to IL-6, we pre viously established that granulocyte macrophage (GM)-colony-stimulatin g factor (CSF) initiates renal injury in autoimmune mice. To determine whether IL-6 could suppress GM-CSF-incited damage, we infused GM-CSF- 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 dis ease.