Effects of viral interleukin 10 introduced by in vivo electroporation on arthrogen-induced arthritis in mice.
OBJECTIVE
Viral interleukin 10 (vIL-10) has a variety of immunomodulatory properties. We examined the applicability of vIL-10 gene transfer to the treatment of mice with arthrogen-collagen-induced arthritis (CIA), which is induced by anti-type II collagen antibodies.


METHODS
One day after anti-type II collagen antibodies were injected into mice, 400 microg of plasmid DNA expressing vIL-10 (pCAGGS-vIL-10) was injected into the bilateral tibialis anterior muscles followed by in vivo electroporation consisting of four 50-ms electric pulses of 100 V (pCAGGS-vIL-10 mice). pCAGGS (400 microg) was similarly injected into control mice (pCAGGS mice).


RESULTS
We observed high serum vIL-10 levels in the pCAGGS-vIL-10 mice, but no vIL-10 was detected in the serum of the pCAGGS mice. Using quantitative real-time polymerase chain reaction, we observed that the ratios of IL-6, tumor necrosis factor-a, and IL-1beta transcripts to those of G6PDH in the joints were significantly lower in the pCAGGS-vIL-10 mice than in the pCAGGS mice (p < 0.05). The pCAGGS-vIL-10 mice showed significant therapeutic effects: the severity of the macroscopic arthritis was significantly suppressed from Days 5 to 21 (p < 0.0001), and the histologically observable development of arthritis was also suppressed in these mice on Day 21 (p < 0.0001).


CONCLUSIONS
These results demonstrated that pCAGGS-vIL-10 gene transfer by in vivo electroporation suppressed arthrogen-CIA.
Kuroda
Takeshi
T
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-Dori, Niigata City, Japan.
Maruyama
Hiroki
H
Shimotori
Masaaki
M
Higuchi
Noboru
N
Kameda
Shigemi
S
Tahara
Hideaki
H
Miyazaki
Jun-Ichi
J
Gejyo
Fumitake
F
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018274:Electroporation; D005814:Genes, Viral; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D007596:Joints / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10