Impact of VIP and cAMP on the regulation of TNF-α and IL-10 production: implications for rheumatoid arthritis

Arthritis Research & Therapy

Richard Williams²  Fionula M Brennan²  Marc Feldmann²  Abhilash Jain¹  Salman Ahmed²  Sarah Field²  Andrew D Foey² 

[1]Department of Musculoskeletal Surgery, Charing Cross Hospital Campus, Imperial College School of Medicine, London, UK

[2]Kennedy Institute of Rheumatology Division, Charing Cross Hospital Campus, Imperial College School of Medicine, London, UK

关键词: VIP;    TNF-α;    T cells;    macrophage;    IL-10;   

Others  :  1101339
DOI  :  10.1186/ar999

 received in 2003-03-14, accepted in 2003-08-11,  发布年份 2003

【 摘 要 】

Vasoactive intestinal peptide (VIP) is an anti-inflammatory immunomodulatory neuropeptide with therapeutic potential demonstrated for collagen-induced arthritis. The aim of this study was to characterise its potential anti-arthritic effect on human monocytes, macrophages, T cells, and rheumatoid arthritis synovial membrane cells. Monocytes, macrophages, and T cells derived from human peripheral blood were treated with VIP and compared with other cAMP-elevating drugs for a range of activating stimuli. Cytokine production was assessed for cell cultures and, in addition, the ability of VIPs to activate cAMP response element binding protein. VIP partially suppressed monocyte- and macrophage-derived tumour necrosis factor α (TNF-α) with no effect on IL-10, whereas VIP fails to regulate IL-10 and TNF-α production by T lymphocytes. No such modulation of cytokine profile was observed for rheumatoid arthritis synovial membrane cells. Elevation of intracellular cAMP, on the other hand, potently suppressed macrophage TNF-α production and modulated T-cell response by inhibiting TNF-α and IFN-γ. VIP's lack of effect on IL-10 and its slight effect on TNF-α results from cAMP being rapidly degraded as the phosphodiesterase IV inhibitor, rolipram, rescues cAMP-dependent activation of cAMP response element binding protein. Interestingly, macrophages stimulated with phorbol 12-myristate 13-acetate/ionomycin displayed an augmented IL-10 response upon addition of dibutyryl cAMP, with corresponding downregulation in TNF-α, suggesting a complex interaction between protein kinase C and protein kinase A in cytokine regulation. In conclusion, VIP may represent an efficaceous anti-arthritic treatment modulating macrophage and T-cell cytokine profiles when used alongside a phosphodiesterase inhibitor.

【 授权许可】

   
2003 Foey et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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