Local and systemic consequences of acute, low-dose ultraviolet B radiation are mediated by different immune regulatory mechanisms.
Acute, low-dose ultraviolet B (UVB) radiation alters the local skin site such that epicutaneous application of hapten fails to induce contact hypersensitivity (CH), but induces tolerance in UVB-susceptible mice. Although the inability of irradiated skin to support CH induction may be a strictly local effect, there may also be systemic immune consequences of UVB radiation delivered in this manner. To examine this matter, abdominal skin of C57BL/6 mice was exposed to acute, low-dose UVB radiation. Dinitrofluorobenzene was immediately painted directly on the irradiated site, or at a distant (unirradiated) site. In separate experiments, epicutaneous application of the hapten on a distant site was delayed for 1-3 days. The mice were tested for acquisition of CH, and for tolerance, i.e. the capacity to become sensitized when exposed subsequently to hapten via normal body wall skin. It was found that, immediately after completion of the UVB regimen, CH was inducible via unirradiated, but not via irradiated, skin. At 3 days post-UVB exposure, CH was no longer inducible even through unirradiated skin. Mice that first encountered hapten via UVB-exposed skin developed tolerance, as did mice that first encountered hapten via unirradiated skin of UVB-treated mice. Neutralizing anti-tumor necrosis factor-alpha TNF-alpha antibodies failed (a) to restore the ability of unirradiated skin to support induction of CH, and (b) to interfere with tolerance induction, whether hapten was first painted on irradiated or unirradiates skin. The data indicate that the acute, low-dose regimen of UVB radiation produces effects on the immune system that are manifest locally as well as systemically. By demonstrating that the disruption of CH induction following UVB radiation is TNF-alpha dependent, whereas locally and systemically induced tolerance is not, our findings encourage further search for other UVB-related modulators of systemic immunity and tolerance.
Shimizu
T
T
Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114.
Streilein
J W
JW
D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000276:immunology; D006241:Haptens / Q000276:immunology; D007108:Immune Tolerance / Q000528:radiation effects*; D007109:Immunity / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000276:immunology / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014466:Ultraviolet Rays / Q000009:adverse effects*
D006241:Haptens; D014409:Tumor Necrosis Factor-alpha; D004139:Dinitrofluorobenzene