ROLE OF INTERLEUKIN-6 IN MEDIATING MESANGIAL CELL-PROLIFERATION AND MATRIX PRODUCTION IN-VIVO

Mesangial cell proliferation and matrix overproduction characterize ma ny progressive glomerular diseases. Based on currently available data, the role of interleukin-6 (IL-6) in mediating mesangial cell prolifer ation and matrix production is controversial. The present study attemp ts to clarify this issue by showing that: (1) IL-6 knock out mice deve lop a normal glomerular architecture and in particular a normal mesang ium (2) Mesangioproliferative glomerulonephritis induced by Habu snake venom is equally severe in IL-6 knock out mice as in control mice. (3 ) A continuous seven-day intraperitoneal infusion of 50 mu g recombina nt human IL-6 into rats with a prior minimal (subnephrito-genic) injur y to mesangial cells does not induce glomerular cell activation, cell proliferation, matrix production, leukocyte influx, platelet influx or proteinuria. (4) A continuous seven-day IL-6 infusion into rats with mesangioproliferative nephritis (anti-Thy 1.1 nephritis) increases mat rix protein transcription in the absence of detectable effects on matr ix protein accumulation and otherwise has no effect on the natural cou rse of the disease. We conclude from these findings that IL-6 is not a n important mediator of mesangial cell proliferation and matrix overpr oduction in vivo, and that currently little rationale exists to advoca te anti-IL-6 therapy in mesangioproliferative disease states.