- Paper Report
- Open Access
VIP therapy of arthritis
- Jose Pablos1
© Biomed Central Ltd 2001
- Received: 25 July 2001
- Accepted: 25 July 2001
- Published: 25 July 2001
- collagen-induced arthritis
- rheumatoid arthritis
- vasoactive intestinal peptide
Vasoactive intestinal peptide (VIP) is a neuropeptide with well known neuroendocrine effects. It is also produced and specifically recognised by cells of the immune system, where VIP may operate as an autocrine or paracrine mediator. In vitro, and in different animal models in vivo, VIP displays a variety of immunomodulatory and anti-inflammatory effects. In these models, VIP shifts T-cell responses toward Th2 and decreases the production of macrophage-derived proinflammatory mediators such as TNF-a, preventing lethal endotoxic shock. These effects make VIP an attractive therapeutic candidate for Th1-mediated inflammatory diseases.
Administration of VIP to mice immunised with collagen II (CII) prevented arthritis development and bone and cartilage destruction. In mice with established disease, VIP administration significantly reduced the severity of arthritis. VIP also prevented adoptive transfer of arthritis by T cells to naive mice. VIP reduced T-cell proliferative responses, decreased IFN-?-secreting T cells, and increased IL-4-secreting T cells in response to CII challenge. VIP also decreased specific IgG2a anti-CII antibodies.
In addition to the immunologic effects of VIP in this model, the authors confirmed a downregulation of proinflammatory cytokines and chemokines, and an upregulation of anti-inflammatory factors (IL-1RA and IL-10) in arthritic tissues of VIP-treated mice or in primary cultures of synovial cells treated with VIP in vitro.
The use of different VIP agonists suggests that the beneficial effects of VIP in this model were mediated by the VIP receptor, VPAC1.
Collagen-induced arthritis in DBA/1 mice; intraperitoneal administration of VIP and agonists PAC1, VPAC1 and VPAC2; histological analysis; analysis of T-cell responses to CII