IMMUNOREACTIVE VASOACTIVE-INTESTINAL-PEPTIDE CONTRIBUTES TO THE IMMUNOSUPPRESSIVE ACTIVITY OF NORMAL AQUEOUS-HUMOR

Suppression of immune-mediated inflammation within the normal anterior chamber (AC) of the eye is in part the result of active suppression o f effector T cell activities by immunosuppressive cytokines found in a queous humor (AqH), the fluid filling the AC. There are immunosuppress ive factors found in the low m.w. fraction (<5 kDa) of AqH, including the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH). In seeking other factors, we now report that the neuropeptide vasoactive intestinal peptide (VIP) is also present in normal AqH. VIP immunoreac tivity was found in normal rabbit eyes at a concentration of 12 +/- 1 nM. At this intraocular concentration, VIP suppressed Ag-stimulated ly mph node cell (LNC) proliferation and IFN-gamma production in vitro. A lthough suppression of LNC proliferation was not neutralized by absorp tion of VIP from the low m.w. fraction of AqH, removal of VIP did neut ralize suppression of IFN-gamma production by this fraction of AqH. Ab sorption of both VIP and alpha-MSH from this fraction of AqH permitted production of IFN-gamma by Ag-stimulated LNC that was no different th an absorbing VIP alone. The low m.w. fraction of AqH absorbed of eithe r alpha-MSH and VIP lost its ability to suppress local adoptive transf er of delayed-type hypersensitivity. The results suggest that VIP is a n important immunosuppressive neuropeptide in AqH. Neuropeptides play an important role in ocular immune privilege and creation of an intrao cular immunosuppressive microenvironment.