Nerve Growth Factor, Neuropeptides, and Mast Cells in Ultraviolet-B-Induced Systemic Suppression of Contact Hypersensitivity Responses in Mice

The induction of systemic immunosuppression following ultraviolet B radiation exposure has been linked with the release of inflammatory and immunomodulatory mediators by cells of the epidermis and dermis. Nerve growth factor has not previously been linked with ultraviolet-B-induced immunosuppressive effects. Nerve growth factor antibodies abrogated ultraviolet-B-induced systemic suppression of contact hypersensitivity responses in BALB/C mice. Subcutaneous injection of nerve growth factor (20 µg per mouse) into dorsal skin 5 d before hapten sensitization on ventral skin suppressed contact hypersensitivity responses in mast-cell-replete but not Wf/Wf mast-cell-depleted mice. Nerve growth factor injected 24 h prior to challenge was not able to suppress the efferent phase of the contact hypersensitivity response. Subcutaneous injection of nerve growth factor (20 µg per mouse) did not suppress contact hypersensitivity responses in capsaicin-pretreated (neuropeptide-depleted) BALB/c mice, and thus sensory c-fibers are necessary for nerve-growth-factor-mediated systemic suppression of contact hypersensitivity responses. Increased concentrations of nerve growth factor within epidermal keratinocytes 8 h after ultraviolet B irradiation were confirmed immunohistochemically. These findings support a role for keratinocyte-derived nerve growth factor via its action on sensory c-fibers, and subsequent release of neuropeptides to mediate mast cell degranulation in systemic suppression of contact hypersensitivity responses in mice following ultraviolet B exposure.