IL-10 in vivo gene expression in a cell-induced animal model of proliferative vitreoretinopathy.
Due to inhibitory activities on cell-mediated immune responses, interleukin-10 (IL-10) has been proposed as a good candidate to treat inflammatory eye disease and proliferative vitreoretinopathy (PVR). In this study we evaluate the effect of human IL-10 (hIL-10) expression in a cell-induced animal model of PVR. Rabbit dermal fibroblasts were genetically modified by infection with retroviral particles carrying the neomycin resistance gene (neoR) alone or in combination with the hIL-10 gene. PVR was induced in rabbits by intravitreal injections of RDF hIL-10 or RDF neo. Some rabbits received instead injections of soluble recombinant hIL-10 (rhIL-10). PVR was graded by fundoscopy. Eyes were enucleated for histology at day 28. ELISA was performed to measure hIL-10 production in RDF supernatants and in vitreous samples, 24 h after injection. Results showed that in vitro hIL-10 production by RDF was 24,500 pg/10(6) cells/ml/24 h. In vivo IL-10 secretion was detected in all rabbits injected with RDF hIL-10 but was undetectable in control rabbits. Similar clinical grades of PVR were found in rabbits injected with RDF hIL-10 or RDF neo. Histology showed that all eyes injected with RDF hIL-10 had significant inflammatory infiltration whereas only one control eye was clearly inflamed. Rabbits injected with soluble rhIL-10 had normal fundoscopy and normal histology. In conclusion, our results show that in vivo, in a cell-induced model of PVR, hIL-10 has no effect in the clinical progression of PVR. Histology, however, shows that pro-inflammatory effects seem to overcome its suppressive properties.
Bali
Ernesto
E
Department of Ophthalmology, CHU St. Pierre, Brussels, Belgium.
Willermain
François
F
Caspers-Velu
Laure
L
Dubois
Christine
C
Dehou
Marie-Françoise
MF
Velu
Thierry
T
Libert
Jacques
J
Bruyns
Catherine
C
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D011817:Rabbits; D018630:Vitreoretinopathy, Proliferative / Q000235:genetics / Q000378:metabolism*
D016753:Interleukin-10