A. Molina et al., ABROGATION OF MERCURIC CHLORIDE-INDUCED NEPHRITIS IN THE BROWN-NORWAYRAT BY TREATMENT WITH ANTIBODIES AGAINST TNF-ALPHA, Mediators of inflammation, 4(6), 1995, pp. 444-451
HgCl2 induces an ailtoimmune disease in the Brown Norway rat character
ized by synthesis of autoantibodies (mainly, anti-GBM Abs), severe pro
teinuria and interstitial nephritis. Also, HgCl2-injected rats develop
glomerular cell infiltrates consisting of ED1(+) cells (monocyte/macr
ophage), starting on day 4 and reaching a maximum on day 8. Treatment
with anti-TNF-alpha antiserum had preventative effects as it reduced t
he urinary protein levels to close to the normal range and also blocke
d the influx of inflammatory cells in the renal glometull and intersti
tium, but circulating anti-GBM and lineal glomerular IgG deposits were
unmodified. In addition, whole isolated glomeruli from HgCl2-lnduced
nephritis secreted TNF-alpha commencing on day 8, being maximally dete
cted on day 11 and preceding, between 2 to 3 days, the development of
proteinuria. The administration of anti-TNF-alpha antiserum or anti-al
pha 4 integrin mAb completely abrogated the synthesis of TNF-alpha in
glomeruli isolated from the respective treated groups of animals, in a
ddition to the proteinuria. Taken together our results confirm that TN
F-alpha plays an important role in the induction and development of Hg
Cl2-induced nephritis and highlights the pathogenic importance ofthe l
ocal release of TNF in those renal diseases in which prominent glomaul
ar macrophage accumulation is a constant feature.