Vol. 283, Issue 1, G115-G121, July 2002
IL-4 inhibits vasoactive intestinal peptide production by
macrophages
Ahmed
Metwali,
Arthur M.
Blum,
David E.
Elliott, and
Joel V.
Weinstock
Division of Gastroenterology-Hepatology, Department of
Internal Medicine, University of Iowa, Iowa City, Iowa 52242
In
schistosomiasis, eggs induce granulomas that have a vasoactive
intestinal peptide (VIP) immunoregulatory circuit. This study explored
the regulation of VIP production at sites of inflammation. Splenocytes
from uninfected C57BL/6 mice expressed VIP mRNA and protein, which
stopped following egg deposition. Eggs induce a Th2 response,
suggesting that Th2 cytokines like interleukin (IL)-4 can regulate VIP.
To address this issue, splenocytes from uninfected mice were incubated
for 4 h with or without recombinant IL-4. IL-4 inhibited
VIP mRNA expression. F4/80+ macrophages were the source of
constitutively expressed VIP, subject to IL-4 regulation. In IL-4
knockout mice, splenic VIP production did not downmodulate during
schistosome infection, suggesting that IL-4 is a critical cytokine
regulating VIP production in wild-type mouse spleen. IL-4-producing
granulomas in schistosomiasis made VIP. Experiments showed that
granuloma VIP derived from F4/80
(nonmacrophage) cell
populations, explaining this paradox. Granuloma F4/80+
cells from IL-4 knockout mice expressed VIP. Thus macrophages can make
VIP, which is subject to IL-4 regulation. However, in the Th2
granulomas, other cell types produce VIP, which compensates for loss of
macrophages as a source of this molecule.
granulomas; interleukin-4; Th1; Th2
