Suppression of Th1 and Th17 Responses and Induction of Treg Responses by IL-18-Expressing Plasmid Gene Combined with IL-4 on Collagen-Induced Arthritis
Effect of pIL-18 combined with rIL4 on CIA mice. Male DBA/1 mice were intradermally immunized with type II collagen emulsified in an equal volume of Freund’s complete adjuvant (FCA) and given intraperitoneal booster injections with type II collagen in PBS after 21 days. At day 28, mice were given intramuscular injections of 10 μg of pIL-18 (alone or in combination with rIL4 or rIL10) or PBS as control, with a booster at the same dosage 14 days later. (a) Mean arthritis macroscopic scores of mice treated with pIL-18 + rIL4 and pIL-18 + rIL10 were significantly lower than the control from day 44 onwards ( versus control by Wilcoxon rank test). Each point represents the mean ± SD of ten mice. (b) Representative histological findings (left: H&E staining ×40; right: Masson staining ×40). Mice were sacrificed on day 60, and ankle and knee joints were removed. The upper two images show severe cartilage surface disruption in CIA mice given the PBS control; the lower two images show intact cartilage surface in CIA mice given pIL-18 combined with rIL4. (c) Representative reverse transcription PCR results showing the expression of IL-18, TNF-α, IL-17A, and IL-10 in CIA mice given the control PBS or pIL-18 combined with rIL4 (60 days after immunization). (d) Changes in the expression of TNF-α, IL-18, IL-10, and IL-17A were determined by real-time PCR. versus control by Student’s -test; versus control by Student’s -test.
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