Effects of increasing UV-B exposure range from an increased incidence of eye disorders (damage to the lens, cornea and retina, and possible intra-ocular melanoma), skin cancers, and infectious diseases. Quantitative estimates of how increased UV-B plays a role in eye damage and skin cancers have already been made. For UV-B effects on the immune system, and as a consequence, the contribution of such effects to the incidence of infectious diseases and tumors, such information is still lacking. The main goal of this project is to investigate the effects of UV-B irradiation on the immune system, and in particular on the resistance to infectuous diseases and tumours. Knowledge obtained during this project will provide the basis for improved risk assessment of increasing UV-B exposure for human health.
Effects of increasing ultraviolet B (UVB) exposure range from an increased incidence of eye disorders (damage to the lens, cornea and retina, and possible intraocular melanoma), skin cancers, and infectious diseases. Quantitative estimates of how increased UVB plays a role in eye damage and skin cancers have already been made. For UVB effects on the immune system, and as a consequence, the contribution of such effects to the incidence of infectious diseases and tumours, such information is still lacking. The main goal of this project is to investigate the effects of UVB irradiation on the immune system, and in particular on the resistance to infectious diseases and tumours.
During this project the effect of UV exposure on the immune system in rodents and partially also in humans was investigated. Several parameters of the immune system or parameters that can influence the immune system such as urocanic acid isomerization and thymidine dimer formation were studied in animal and man. Dose dependency and kinetics of the UVB induced effects were studied using animal models. In general the natural killer cell function and the mixed lymphocyte response were inhibited by UVB exposure in animal and man. In animals the effect of the UVB induced immune alteration on the resistance against infectious diseases and tumours was studied. During photocarcinogenesis several parameters of the immune system were altered in the skin, draining lymph nodes and spleen. In addition, the UV induced immunosuppression resulted in a decreased resistance against skin associated and nonskin associated infectious diseases in rodents. The doses of UV needed for these alterations was only a suberythemal doses. The project is continuing.
For estimation of risk associated with UV-B exposure it is necessary to make an inventory of such effects on the immune system and on the related resistance to infectious diseases and tumours. The project starts with the investigation of UV-B induced effects on several basal immune parameters in different species such as mice, rats, and humans. Basal immune parameters that are investigated comprise: natural killer cell function, mitogenic responsiveness, mixed lymphocyte responses, determination of immunoglobulin titers, immunohistopathology of the skin, etc.
Following these initiating studies, experiments will be performed to study whether mediators/photoreceptors such as uricanic acid isomers are involved in UV-B induced changes of the immune system.
Finally, studies will be performed with regard to effects of UV-B to the resistance/immunity against local skin-associated and non-skin-associated infectious diseases and tumours in rodents. Herpes simplex infection will be studied as an example of a skin-associated infectious disease. For the study with respect to non-skin associated infectuous diseases a parasitic infection model (Trichinella spiralis), a bacterial infection model (Listeria monocytogenes) and a viral infection model (rat cytomegalo virus) are available.
Funding SchemeCSC - Cost-sharing contracts
3508 GA Utrecht
EH8 9AG Edinburgh
DD1 9SY Dundee