Academic journal article Bulletin of the World Health Organization

Immunosuppression Induced by Ultraviolet Radiation: Relevance to Public Health. (Public Health Classics)

Academic journal article Bulletin of the World Health Organization

Immunosuppression Induced by Ultraviolet Radiation: Relevance to Public Health. (Public Health Classics)

Article excerpt

The article by Fisher & Kripke (1), published 25 years ago, is a seminal one as it represents the first occasion on which ultraviolet radiation (UVR) was demonstrated to have systemic suppressive effects on the immune system. It marked the initiation of an exciting and fast-moving area known as "photoimmunology" and has led to important advances in understanding how the immune system of the skin operates. The findings have had far-reaching implications for diverse issues including skin cancers, infectious diseases, sunscreens and phototherapy.

Experiments in mice in the early 1970s had shown that chronic UVR over a period of several months led to the induction of skin cancers. These tumours, unlike most other turnouts, were highly antigenic, as shown by their rejection on transplantation to recipient mice of the same genetic background. So, how could they arise and grow progressively in the original animals? Fisher & Kripke had found previously that, if mice were ultraviolet (UV) irradiated for a period insufficiently long to induce primary skin tumours and then received the transplants, the tumours were not rejected (2). In the paper discussed here, the alteration induced by the short-term UV exposure in the recipient mice was shown to be immunological in nature and was systemic. This was revealed by three types of experiments described in the article. On the basis of the results of these experiments the authors concluded that UVR can prevent an immunological mechanism that normally eliminates nascent tumour cells in the skin.

The sequence of steps leading to UV-induced systemic immunosuppression was not established and, indeed, has not been fully explained, even today. Fisher & Kripke speculated that the production of soluble "antigens" in response to the skin damage caused by UVR could lead to the generation of suppressor cells, rather than effector cells. It is now known that various photoreceptors located in the upper layers of the skin, of which DNA and urocanic acid are probably the most important, absorb UVR, alter their structure as a result, and then initiate the production of a series of immunological mediators, both locally and systemically, as well as phenotypic changes in the skin and lymph nodes. The end result is the induction of particular subsets oft regulatory cells which down-regulate cell-mediated immunity (3). The evolutionary explanation of such a response to UVR may be to prevent the altered molecules being recognized as "non-self" neoantigens. If immune responses were generated routinely to these molecules or to the cells in which they were located, this might result in chronically inflamed skin. Thus the immunomodulation which follows UVR may be desirable under many circumstances. Where it might not be desirable is in the case of a skin tumour or infection.

The most serious adverse health effect of UVR is the development of skin cancers. Excess sun exposure increases the risk of both non-melanoma (squamous cell carcinoma (SCC) and basal cell carcinoma (BCC)) and melanoma skin cancers. It has been estimated by the United Nations Environment Panel that, in the past few years, over 2 million cases of non-melanoma and 200 000 cases of malignant melanoma have occurred annually in the world. The incidence of both BCCs and SCCs in white-skinned people living in temperate countries and places nearer the equator has increased in the past 30 years, in many surveys by two- or threefold. Similarly the incidence of malignant melanomas and mortality rates have risen sharply in recent decades in whites, although not in blacks. This tumour is less common than BCCs or SCCs but causes 80% of the deaths associated with skin cancer.

The critical role of the normal host defence mechanism in preventing skin cancer is shown dramatically in immuno-compromised individals, such as patients with kidney transplants, who are at significantly increased risk of developing cutaneous malignancies, especially SCCs, on sun-exposed parts of their bodies, such as the face and the back of the hands (4). …

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