ABSTRACT
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259 Photoimmune Suppression: Basic Phenomena . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260 Photoreceptors in the Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261 Urocanic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262 Oxidized Phospholipids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
Transmission of the Immune Suppressive Signal from the Skin to the Immune System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
Antigen Presenting Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263 UV-Induced Cytokines and Biological Response Modifi ers . . . . . . . . . . . . . 265
T Suppressor Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267 CD4+CD25+ T Regulatory Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267 NKT Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
Summary and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
Immunotoxicity is generally defi ned as “the study of adverse effects on the immune system resulting directly from environmental, occupational, or therapeutic exposure to chemicals, biological materials, and in certain instances, physiological factors, collectively referred to as agents. It encompasses immunosuppression, allergy, autoimmunity and infl ammation.”1 Although drugs, volatile organic chemicals, arsenic, lead, and 2,3,7,8-Tetrachlorodibenzo-p-dioxin readily come to mind when considering agents that
induce immune toxicity, the immunotoxic agent that all humans come into contact with on a daily basis is the ultraviolet (UV) radiation (290 to 400 nm) found in sunlight. UV radiation is best known as the primary etiologic agent in the development of skin cancer and it is clear that the immune suppression induced by UV radiation is a major risk factor for skin cancer induction. In addition, UV exposure has been shown to suppress the immune response to microbial, fungal, and viral antigens. Because of the association between skin cancer induction and immune suppression, research efforts regarding the adverse effects of UV radiation has been the focus of dermatologists, cancer biologists and immunologists, but generally, not toxicologists. One can argue, however, that UV radiation is the oldest and most prevalent immunotoxin in our environment. Exposure to UV radiation induces immune suppression, as well as infl ammation, and in some cases can contribute to allergic reactions, so it fi ts the defi nition of an immunotoxic agent. UV exposure suppresses the immune response in almost all vertebrate animal species tested so far, from fi sh to humans. The mechanisms involved appear to be very similar from species to species and doses of UV radiation that induce immune suppression in man compare well to those that suppress in experimental animal species. Immune suppression can be induced after chronic exposure, or after a single exposure to a relatively low dose (i.e., the amount required to cause distinct “redness” of Type 1 Caucasian skin, the minimal erythemal dose) of UV radiation. The focus of this chapter is to review the mechanisms by which this “granddaddy of all immunotoxins” suppresses the immune response.
