Vasoactive Intestinal Peptide (VIP) Prevents Experimental Arthritis
VIP is a neuropeptide that has anti-inflammatory and immuno-modulatory properties. Its ability to suppress and prevent experimentally induced arthritis was reported by Delgado et al in Nature Medicine 7:563, 2001. Collagen-induced arthritis (CIA) was induced in mice by immunizing with type II collagen. VIP or placebo was administered intraperitoneally daily or on alternate days for two weeks.
Results: Mice treated with VIP showed delayed onset, lower incidence and decreased severity of CIA in comparison with placebo-treated arthritic mice. Histologically, there was profound reduction of inflammatory infiltrate, pannus formation, cartilage destruction and bone erosion. The mechanism of VIP’s effect was explored. VIP treatment was associated with the following:
- inhibition of T-cell clonal expansion in response to type II collage challenge;
- downregulation in Th1 cytokine production (e.g., interferon-gamma), and increase in Th2 cytokine production (e.g., IL-4);
- suppression of type II collagen-specific IgG antibodies;
- reduction of the CD4:CD8 ratio in synovium;
- suppression of inflammatory cytokines (e.g., tumor necrosis factor and interleukin-1) and upregulation of anti-inflammatory cytokines (e.g., interleukin-10 and interleukin-1 receptor antagonist);
- suppression of MMP-2 gelatinase expression and activity.
Conclusion: VIP has a therapeutic effect on an animal model of rheumatoid arthritis. This therapeutic effect is associated with downregulation of both inflammatory and autoimmune components of the disease. These results suggest that VIP could be a viable candidate for clinical investigation in rheumatoid arthritis.
Editorial Comment: These results are very exciting. There are few treatments that have been shown to have such broad effects. For example, the inhibitors of TNF and IL-1 target inflammatory cascades but not immune pathways, while immunosuppressives do the opposite. These investigators show that VIP, in contrast, has profound inhibitory effects on both autoimmune pathways and inflammatory cascades. To the extent that human RA may mimic CIA in being a disease of uncontrolled Th1-type responses, this broad approach of inhibiting both pathways has great appeal.
