VIP and PACAP down-regulate CXCL10 (IP-10) and up-regulate CCL22 (MDC) in spleen cells

The immunoregulatory neuropeptides VIP and PACAP favor Th2-type immune responses. Antigen-stimulated Th2 cells produce VIP, VIP/PACAP induce Th2 cytokine responses, and promote the preferential survival of Th2 effectors. In this study, we investigate the effects of VIP/PACAP on two chemokines, i.e. CXCL10 (IP-10) acting on CXCR3 expressed on activated Th1 cells, and CCL22 (MDC) acting on CCR4 and 8 expressed on activated Th2 cells. VIP and PACAP down-regulate CXCL10, and up-regulate CCL22 in vivo and in vitro. The effects on the two chemokines appear to be different in mechanistic terms. The fact that VIP/PACAP might promote the directed migration of Th2 cells adds a new dimension to their participation in the Th2 auto-regulatory loop.