The Neuropeptides VIP / PACAP and T Cells: Inhibitors or Activators?

Author(s): Doina Ganea , Mario Delgado .

Journal Name: Current Pharmaceutical Design

Volume 9 , Issue 12 , 2003

Abstract:

The structurally related neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are released within the lymphoid organs following antigenic stimulation, and modulate the function of inflammatory cells through specific receptors. In activated macrophages, VIP and PACAP inhibit the expression at both mRNA and protein level of pro-inflammatory cytokines and chemokines, through effects on de novo expression or nuclear translocation of a number of transcription factors, i.e. NFkB, CREB, c-Jun, JunB, and IRF-1. In addition, VIP and PACAP promote Th2-type, and inhibit Th1-type responses in vivo and in vitro, through several mechanisms, including preferential survival of Th2 effectors and subsequent generation of Th2 memory cells. The function of VIP / PACAP as “macrophage deactivating factors” appears to be responsible for their protective effect in vivo in models of septic shock. Both deactivation of macrophages and inhibition of Th1-type responses appear to be responsible for the beneficial effect of VIP/PACAP in models of Th1-type autoimmune diseases such as rheumatoid arthritis.

Keywords: neuropeptides, vasoactive intestinal peptide, pituitary adenylate cyclase activating polypeptide, effector cells, macrophages

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Article Details

VOLUME: 9
ISSUE: 12
Year: 2003
Page: [997 - 1004]
Pages: 8
DOI: 10.2174/1381612033455116
Price: $58

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