title: Effect of interleukin-10 treatment on crescentic glomerulonephritis in rats.
abstract: This study examined the utility of interleukin-10 (IL-10), a cytokine with potent anti-macrophage and anti-Th1 activity, in the treatment of experimental anti-glomerular basement membrane (GBM) nephritis in the rat. Accelerated anti-GBM disease was induced in Sprague-Dawley rats by immunization with rabbit IgG, followed five days later by an i.v. injection of anti-GBM serum. Groups of four rats received daily s.c. injections of recombinant mouse IL-10 (500, 10 or 0.2 microgram/kg/day) or saline (control) from the time of anti-GBM serum administration until being killed on day 14. IL-10 treatment suppressed the skin DTH response as measured by skin thickness (44 to 62% decrease vs. control, p < 0.05). Compared to saline controls, IL-10 treatment had no beneficial effect on renal function, proteinuria or histological damage (including crescent formation) at any dose examined. A detailed analysis of high dose IL-10 (500 micrograms/kg/day) and saline treated animals was undertaken. Saline controls had marked glomerular macrophage accumulation and proliferation, which was augmented by IL-10 treatment (46 to 99% increases and 44 to 143% increases, respectively; p < 0.05). Immunohistochemical staining found no difference in the state of macrophage activation between the groups, as determined by the percentage of macrophages expressing IL-1 beta protein. Northern blot analysis of whole kidney RNA demonstrated an 830% increase in IL-1 beta mRNA expression in saline controls compared to normal rat kidney. High dose IL-10 treatment reduced IL-1 beta mRNA levels by 60% compared to controls (P < 0.05), but did not significantly reduce glomerular IL-1 beta protein expression. IL-10 treatment increased serum levels of rat anti-rabbit IgG, induced a rat anti-mouse IL-10 response and augmented glomerular deposition of rat C3. In conclusion, IL-10 was not an effective treatment for rat crescentic anti-GBM glomerulonephritis. This may have been due to the failure of IL-10 to achieve a sufficient reduction in IL-1 beta expression and macrophage participation in disease, or promotion of the Th2 immune response.
authors.affiliation: Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Chadban
authors.forename: G H
authors.initials: GH
authors.lastname: Tesch
authors.forename: H Y
authors.initials: HY
authors.lastname: Lan
authors.forename: R C
authors.initials: RC
authors.lastname: Atkins
authors.forename: D J
authors.initials: DJ
authors.lastname: Nikolic-Paterson
mesh_terms: D000818:Animals; D000917:Antibody Formation; D016207:Cytokines / Q000096:biosynthesis; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006968:Hypersensitivity, Delayed / Q000175:diagnosis; D016753:Interleukin-10 / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology; D007958:Leukocyte Count / Q000187:drug effects; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012885:Skinfold Thickness
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D016753:Interleukin-10