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Somatostatin Is an Immunosuppressive Factor in Aqueous Humor

¹From the Schepens Eye Research Institute and the ²Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.

PURPOSE. To detect the presence of somatostatin (SOM) in normal aqueous humor and to characterize its immunosuppressive activity.

METHODS. Fresh rabbit aqueous humor was assayed for SOM by competitive ELISA. Primed T cells stimulated through their T-cell receptor (TCR) were treated with SOM at concentrations that ranged the level of SOM found in normal aqueous humor. The T cells were assayed for proliferation, lymphokine production, and immunosuppressive activity.

RESULTS. Normal rabbit aqueous humor contained 196 ± 45 pg/mL (10^-10 M) of SOM. At concentrations between 10 and 300 pg/mL, SOM suppressed IFN- production by TCR-stimulated primed T cells in culture. Frozen and thawed aqueous humor depleted of SOM no longer suppressed IFN- production by the TCR-stimulated primed T cells. SOM induced TGF-ß but not IL-4 production, nor did it suppress proliferation by TCR-stimulated primed T cells. The SOM-treated T cells functioned as regulatory T cells, and this regulatory activity was neutralized by anti--MSH antibodies. Furthermore, SOM induced -MSH production by the TCR-stimulated primed T cells.

CONCLUSIONS. SOM is present in aqueous humor and contributes to the immunosuppressive activity of aqueous humor. Moreover, SOM induces the production of the potent immunomodulating factor -MSH by TCR-stimulated primed T cells through which the SOM-treated T cells suppress other T cells. Thus, SOM can contribute to the ocular immunosuppressive microenvironment by promoting the production of immunosuppressive cytokines and inducing the activation of regulatory T cells.

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