Group III received a combined treatment of MSC and IL-4, while group IV served as a CIA diseased control group receiving phosphate buffer saline (PBS).
This is the first report where quercetin was shown to modulate the immune response to arthritis via attenuation of the purinergic system (E-NTPDase and E-ADA activities) and the levels of IFN-gamma and IL-4.
In the collagen-induced model of arthritis, GCSF-F8 and F8-IL3 induced a worsening of the disease, while F8-IL4-F8 slowed arthritis progression but, surprisingly, exhibited substantial toxicity when used in combination with dexamethasone.
Our findings indicate that pIL-18 gene combined with IL-4 ameliorates arthritis in the CIA mouse by suppression of Th1 and Th17 cytokines and increasing expression of FoxP3 and GATA-3.
The light microscopical evaluation of paws with arthritis revealed a predominant infiltration of neutrophils, which substantially decreased 24 h after treatment with F8-IL4 and DXM.
The arthritis-alleviative effects were closely associated with the augmentation of IL-4, IL-10, and collagen-specific IgG1, and with the distinct reduction of IFN-γ, collagen-specific IgG2a, and the marked decrease of proinflammatory cytokines IL-6, IL-17, and TNF-α and RANKL.
DBA/1 mice doubly deficient in IL-4 and IL-10 were used to confirm that these two cytokines are important for the APL-induced attenuation of arthritis.
Besides its responsiveness, the promoter strength proved sufficient for generating therapeutically efficacious levels interleukin-4, as demonstrated by the successful protection against cartilage erosion in collagen-induced arthritis.
Protective effects were observed in CIA rats by injecting these recombinant DNA vaccines, which could alleviate arthritis index, decrease the levels of IFN-gamma and anti-CII antibody in serum, and increase the levels of IL-4.
Immunization of mice, lacking IL-4 and Stat6, with proteoglycan results in a significant increase in arthritis severity in comparison to wild-type controls, suggesting that arthritis severity is regulated by IL-4 through a Stat6-dependent mechanism.
Here, we report that local overexpression of IL-4, introduced by a recombinant human type 5 adenovirus vector (Ad5E1mIL-4) prevents joint damage and bone erosion in the knees of mice with collagen arthritis (CIA).
TNF-alpha and IL-1beta promote leukocyte recruitment to arthritic joints and may contribute to cartilage degradation while regulatory cytokines such as IL-4 and IL-1RA may in part determine the course of arthritis.
To determine the efficacy of intra-articular IL-4 gene therapy in an animal model of arthritis using a retroviral vector, a retrovirus encoding rat IL-4 (DA-IL-4) was engineered, purified and concentrated to high titer (>/=109 CFU/ml).
New studies of streptococcal cell wall arthritis in rats demonstrated that beta 1 integrin-mediated cell-matrix interactions are involved in the induction and perpetuation of inflammatory synovitis and that systemic administration of interleukin-4 selectively suppresses established synovitis, presumably by effects on monocyte function.