Recent investigations in our laboratory have shown that murine intesti
nal smooth muscle cells (ISMCs) can exert an immunomodulatory effect o
n T-cells. Therefore, we examined the effects of substance P, calciton
in gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP)
on the ability of ISMCs to modulate T-cell proliferation and lymphoki
ne generation. T-cell proliferation was observed when these cells were
co-cultured with IFN-pretreated C57/BL6 ISMCs which expressed major h
istocompatibility complex II (MHC II), but not during T-cell co-cultur
e with C2D (MHC II -/-)ISMCs pretreated in the same manner. T-cell pro
liferation during co-culture with C57/BL6 ISMCs was also associated wi
th significantly enhanced T-cell synthesis of IFN. When CGRP (at 10(-9
) M), but not substance P or VIP, was added to C57/BL6 ISMCs during th
e IFN-pretreatment period, T-cell proliferation was significantly incr
eased. However, increased T-cell proliferation was not observed if the
concentration of CGRP was increased to 10(-6) M. At the higher concen
tration, addition of substance P or VIP during the pretreatment period
significantly inhibited the subsequent T-cell proliferation. Pretreat
ment of C57/BL6 ISMCs with any of the three neuropeptides and IFN resu
lted in the diminished production of IL-4 and IFN by co-cultured T-cel
ls. A similar pattern of cytokine secretion was observed during T-cell
co-culture with IFN- and neuropeptide-pretreated C2D ISMCs except whe
n 10(-6) M substance P was added; IFN secretion by co-cultured T-cells
was increased 4-fold under these conditions. Taken together, these da
ta show a direct modulatory role for neuropeptides in the interaction
between ISMCs and T-cells and suggest that, in general, neuropeptides
may dampen immune responses in the neuromuscular layers of the inflame
d intestine.