A gene transfer system establishes interleukin-6 neither promotes nor suppresses 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 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.
Naito
T
T
Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston 02115, USA.
Yokoyama
H
H
Moore
K J
KJ
Dranoff
G
G
Mulligan
R C
RC
Kelley
V R
VR
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology*; D017690:Cell Transplantation; D005260:Female; D018014:Gene Transfer Techniques; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr
D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor