Human health in relation to exposure to solar ultraviolet radiation under changing stratospheric ozone and climate.

The Montreal Protocol has limited increases in the UV-B (280-315 nm) radiation reaching the Earth's surface as a result of depletion of stratospheric ozone. Nevertheless, the incidence of skin cancers continues to increase in most light-skinned populations, probably due mainly to risky sun exposure behaviour. In locations with strong sun protection programs of long duration, incidence is now reducing in younger age groups. Changes in the epidemiology of UV-induced eye diseases are less clear, due to a lack of data. Exposure to UV radiation plays a role in the development of cataracts, pterygium and possibly age-related macular degeneration; these are major causes of visual impairment world-wide. Photodermatoses and phototoxic reactions to drugs are not uncommon; management of the latter includes recognition of the risks by the prescribing physician. Exposure to UV radiation has benefits for health through the production of vitamin D in the skin and modulation of immune function. The latter has benefits for skin diseases such as psoriasis and possibly for systemic autoimmune diseases such as multiple sclerosis. The health risks of sun exposure can be mitigated through appropriate sun protection, such as clothing with both good UV-blocking characteristics and adequate skin coverage, sunglasses, shade, and sunscreen. New sunscreen preparations provide protection against a broader spectrum of solar radiation, but it is not clear that this has benefits for health. Gaps in knowledge make it difficult to derive evidence-based sun protection advice that balances the risks and benefits of sun exposure.

Environmental effects of ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2017.

The Environmental Effects Assessment Panel (EEAP) is one of three Panels of experts that inform the Parties to the Montreal Protocol. The EEAP focuses on the effects of UV radiation on human health, terrestrial and aquatic ecosystems, air quality, and materials, as well as on the interactive effects of UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously held. Because of the Montreal Protocol, there are now indications of the beginnings of a recovery of stratospheric ozone, although the time required to reach levels like those before the 1960s is still uncertain, particularly as the effects of stratospheric ozone on climate change and vice versa, are not yet fully understood. Some regions will likely receive enhanced levels of UV radiation, while other areas will likely experience a reduction in UV radiation as ozone- and climate-driven changes affect the amounts of UV radiation reaching the Earth's surface. Like the other Panels, the EEAP produces detailed Quadrennial Reports every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Update Reports of recent and relevant scientific findings. The most recent of these was for 2016 (Photochem. Photobiol. Sci., 2017, 16, 107-145). The present 2017 Update Report assesses some of the highlights and new insights about the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. A full 2018 Quadrennial Assessment, will be made available in 2018/2019.

The influence of HIV infection on the age dependence of squamous cell carcinoma of the skin in South Africa.

BACKGROUND: Cancer incidence typically increases with age, but it is not known whether ethnic characteristics influence the age dependence of squamous cell carcinoma of the skin (SCC). OBJECTIVES: (i) To determine the age dependence of SCC in the black African, coloured and white population groups of South Africa (SA); and (ii) to show whether any differences in the rate of change of age dependence could be influenced by diversity in behaviour and lifestyle, especially with regard to the prevalence of HIV infection, rather than by a fundamental variation in cancer biology between the populations. METHODS: Linear regression analysis was applied to the logarithm of the age-specific incidence rates for SCC v. the logarithm of age between 35 and 74 years. The slopes of the regression (age exponent) were compared for each subset of gender, population group and year of diagnosis (between 2000 and 2010). RESULTS: The most notable feature was the low value of the age exponent in both male and female black African compared with the white and coloured populations. This finding could be explained in part by the difference in the prevalence of HIV infection in the black African population group compared with the white and coloured population groups. CONCLUSIONS: The prevalence of HIV infection in black Africans in SA tends to decrease the apparent age component in SCC compared with the white and coloured population groups. Other factors relating to lifestyle and behaviour that differ between the population groups are also likely to influence the age component in SCC.

The influence of HIV infection on the age dependence of squamous cell carcinoma of the skin in South Africa

Background. Cancer incidence typically increases with age, but it is not known whether ethnic characteristics influence the age dependence of squamous cell carcinoma of the skin (SCC).Objectives. (i) To determine the age dependence of SCC in the black African, coloured and white population groups of South Africa (SA); and (ii) to show whether any differences in the rate of change of age dependence could be influenced by diversity in behaviour and lifestyle, especially with regard to the prevalence of HIV infection, rather than by a fundamental variation in cancer biology between the populations.Methods. Linear regression analysis was applied to the logarithm of the age-specific incidence rates for SCC v. the logarithm of age between 35 and 74 years. The slopes of the regression (age exponent) were compared for each subset of gender, population group and year of diagnosis (between 2000 and 2010).Results. The most notable feature was the low value of the age exponent in both male and female black African compared with the white and coloured populations. This finding could be explained in part by the difference in the prevalence of HIV infection in the black African population group compared with the white and coloured population groups.Conclusions. The prevalence of HIV infection in black Africans in SA tends to decrease the apparent age component in SCC compared with the white and coloured population groups. Other factors relating to lifestyle and behaviour that differ between the population groups are also likely to influence the age component in SCC

The consequences for human health of stratospheric ozone depletion in association with other environmental factors.

Due to the implementation of the Montreal Protocol, which has limited, and is now probably reversing, the depletion of the stratospheric ozone layer, only modest increases in solar UV-B radiation at the surface of the Earth have occurred. For many fair-skinned populations, changing behaviour with regard to exposure to the sun over the past half century - more time in the sun, less clothing cover (more skin exposed), and preference for a tan - has probably contributed more to greater levels of exposure to UV-B radiation than ozone depletion. Exposure to UV-B radiation has both adverse and beneficial effects on human health. This report focuses on an assessment of the evidence regarding these outcomes that has been published since our previous report in 2010. The skin and eyes are the organs exposed to solar UV radiation. Excessive solar irradiation causes skin cancer, including cutaneous malignant melanoma and the non-melanoma skin cancers, basal cell carcinoma and squamous cell carcinoma, and contributes to the development of other rare skin cancers such as Merkel cell carcinoma. Although the incidence of melanoma continues to increase in many countries, in some locations, primarily those with strong sun protection programmes, incidence has stabilised or decreased over the past 5 years, particularly in younger age-groups. However, the incidence of non-melanoma skin cancers is still increasing in most locations. Exposure of the skin to the sun also induces systemic immune suppression that may have adverse effects on health, such as through the reactivation of latent viral infections, but also beneficial effects through suppression of autoimmune reactivity. Solar UV-B radiation damages the eyes, causing cataracts and pterygium. UV-B irradiation of the skin is the main source of vitamin D in many geographic locations. Vitamin D plays a critical role in the maintenance of calcium homeostasis in the body; severe deficiency causes the bone diseases, rickets in children and osteomalacia in adults. Although many studies have implicated vitamin D deficiency in a wide range of diseases, such as cancer and cardiovascular disease, more recent evidence is less compelling, with meta-analyses of supplementation trials failing to show a beneficial effect on the health outcomes that have been tested. It continues to be difficult to provide public health messages to guide safe exposure to the sun that are accurate, simple, and can be used by people with different skin types, in different locations, and for different times of the year or day. There is increasing interest in relating sun protection messages to the UV Index. Current sun protection strategies are outlined and assessed. Climatic factors affect the amount of UV radiation received by the skin and eyes, separately from the effect of ozone depletion. For example, cloud cover can decrease or increase the intensity of UV radiation at Earth's surface and warmer temperatures and changes in precipitation patterns may alter the amount of time people spend outdoors and their choice of clothing. The combination of changes in climate and UV radiation may affect the number of pathogenic microorganisms in surface waters, and could have an impact on food security through effects on plant and aquatic systems. It remains difficult to quantify these effects and their possible importance for human health.

Does vitamin D protect against respiratory viral infections?

The active form of vitamin D has effects on both innate and adaptive immune responses that may influence the outcome in many infectious diseases. Observational studies conclusively show that a low vitamin D status is associated with an increased occurrence of respiratory viral infections, which globally represent significant health and financial burdens. However, no consistent protective effects are evident in prospective clinical trials carried out to date where vitamin D was provided as a dietary supplement, except possibly in cases where the starting vitamin D status of the individual was considered deficient. Thus far, vitamin D has not been found to enhance the immune response to vaccines. The design of future prospective clinical trials assessing a role for vitamin D in respiratory viral infections requires very careful planning to avoid the uncertainties associated with the data available currently.

Human health impacts in a changing South African climate.

Climate change is projected to lead to warmer temperatures, especially in southern Africa, where the warming is predicted to be 2°C higher than the global increase. Given the high burden of disease already associated with environmental factors in this region, this temperature increase may lead to grave challenges for human health and quality of life. HIV/AIDS, poverty, food and water insecurity together with inequality and unemployment will further complicate the manner in which we will need to address the challenges of a changing climate. The health impacts are direct, such as increased temperatures leading to heat exhaustion, and indirect, such as likely increases in infectious diseases from contaminated water and changes in the distribution and/or magnitude of vector-borne diseases. The most effective measures for adapting to climate change to ensure healthy populations are to implement basic public health systems and services. These range from a continuous supply of clean water to adequate primary healthcare services. Support for required interventions is required not only from government, but also from healthcare professionals and communities. The need for disease surveillance, data capturing and more focused research is paramount.

Dietary vitamin D alters the response of the skin to UVB-irradiation depending on the genetic background of the mice.

Ultraviolet B (UVB) irradiation of the skin has the benefit of causing the local production of previtamin D3 but also results in cutaneous DNA damage and suppression of the skin immune system (SIS). Strains of mice differ in their ability to be suppressed by UVB irradiation: BALB/c mice are considered "resistant" and C57BL/6 "sensitive". This study evaluated whether vitamin D-replete (D+) and deficient (D-) BALB/c and C57BL/6 mice differed in their cutaneous response to UVB irradiation. Immunosuppression was assessed by measuring the contact hypersensitivity (CHS) response, DNA damage and repair determined by counting thymine dimer positive keratinocyte nuclei, and cutaneous inflammation and epidermal hyperplasia evaluated by light microscopy. The suppression in the CHS response induced by the UVB irradiation was reduced in the D+ C57BL/6 mice compared with the D- C57BL/6 mice. Similarly there was a reduction in DNA damage and promotion of its repair in the D+ C57BL/6 mice compared with the D- C57BL/6 mice. A reduction in inflammation in female D+ C57BL/6 mice compared with D- C57BL/6 females also occurred. In contrast, the suppression in the CHS response, DNA damage and its repair, and inflammation induced by UVB irradiation were similar in the D+ and D- BALB/c mice. These results indicate that dietary vitamin D3 can reduce UVB-induced suppression of the CHS response depending on the genetic background of the mice, an effect that may relate to the reduction in DNA damage and an increase in its rate of repair.

The distribution of immune cells in the lungs of classical and atypical ovine pulmonary adenocarcinoma.

Ovine pulmonary adenocarcinoma (OPA) is a contagious tumour caused by infection of sheep with Jaagsiekte sheep retrovirus. Two forms of OPA have been identified, classical and atypical, which can be distinguished clinically and pathologically. Most notably classical OPA is progressive until death, while atypical OPA remains subclinical. In the present study the local immune responses in the lungs of cases of atypical OPA were compared with those from classical cases by immunohistochemistry using a panel of mouse anti-sheep mAbs. Distinct differences in the distribution of immune cell subsets in the two forms of OPA were observed. In particular there was an intratumoural influx of T cell subsets and MHC Class II expression on the tumour cells in atypical OPA, neither of which was seen in classical OPA. It is possible that these differences may contribute, at least in part, to determining the progressive course of classical OPA compared with the subclinical nature of atypical OPA.

The human health effects of ozone depletion and interactions with climate change.

Depletion of the stratospheric ozone layer has led to increased solar UV-B radiation (280-315 nm) at the surface of the Earth. This change is likely to have had an impact on human exposure to UV-B radiation with consequential detrimental and beneficial effects on health, although behavioural changes in society over the past 60 years or so with regard to sun exposure are of considerable importance. The present report concentrates on information published since our previous report in 2007. The adverse effects of UV radiation are primarily on the eye and the skin. While solar UV radiation is a recognised risk factor for some types of cataract and for pterygium, the evidence is less strong, although increasing, for ocular melanoma, and is equivocal at present for age-related macular degeneration. For the skin, the most common harmful outcome is skin cancer, including melanoma and the non-melanoma skin cancers, basal cell carcinoma and squamous cell carcinoma. The incidence of all three of these tumours has risen significantly over the past five decades, particularly in people with fair skin, and is projected to continue to increase, thus posing a significant world-wide health burden. Overexposure to the sun is the major identified environmental risk factor in skin cancer, in association with various genetic risk factors and immune effects. Suppression of some aspects of immunity follows exposure to UV radiation and the consequences of this modulation for the immune control of infectious diseases, for vaccination and for tumours, are additional concerns. In a common sun allergy (polymorphic light eruption), there is an imbalance in the immune response to UV radiation, resulting in a sun-evoked rash. The major health benefit of exposure to solar UV-B radiation is the production of vitamin D. Vitamin D plays a crucial role in bone metabolism and is also implicated in protection against a wide range of diseases. Although there is some evidence supporting protective effects for a range of internal cancers, this is not yet conclusive, but strongest for colorectal cancer, at present. A role for vitamin D in protection against several autoimmune diseases has been studied, with the most convincing results to date for multiple sclerosis. Vitamin D is starting to be assessed for its protective properties against several infectious and coronary diseases. Current methods for protecting the eye and the skin from the adverse effects of solar UV radiation are evaluated, including seeking shade, wearing protective clothing and sunglasses, and using sunscreens. Newer possibilities are considered such as creams that repair UV-induced DNA damage, and substances applied topically to the skin or eaten in the diet that protect against some of the detrimental effects of sun exposure. It is difficult to provide easily understandable public health messages regarding "safe" sun exposure, so that the positive effects of vitamin D production are balanced against the negative effects of excessive exposure. The international response to ozone depletion has included the development and deployment of replacement technologies and chemicals. To date, limited evidence suggests that substitutes for the ozone-depleting substances do not have significant effects on human health. In addition to stratospheric ozone depletion, climate change is predicted to affect human health, and potential interactions between these two parameters are considered. These include altering the risk of developing skin tumours, infectious diseases and various skin diseases, in addition to altering the efficiency by which pathogenic microorganisms are inactivated in the environment.

Does chronic sunscreen use reduce vitamin D production to insufficient levels?

Exposure to ultraviolet B radiation in sunlight provides the mechanism for more than 90% of the vitamin D production in most individuals. Concern has been expressed in recent years that the widespread use of sunscreens, particularly those with high sun protection factors, may lead to a significant decrease in solar-induced previtamin D(3) in the skin, resulting in a vitamin D level which is considered insufficient for protection against a wide range of diseases. In this article the published evidence to support and to question this view is presented. It is concluded that, although sunscreens can significantly reduce the production of vitamin D under very strictly controlled conditions, their normal usage does not generally result in vitamin D insufficiency.

Suberythemal ultraviolet B radiation alters the expression of cell cycle-related proteins in the epidermis of human subjects without leading to photoprotection.

BACKGROUND: Deregulation of the cell cycle proteins is one of the critical factors leading to cutaneous carcinogenesis. OBJECTIVES: To monitor the expression of cell cycle proteins in the epidermis of subjects after repeated exposure to ultraviolet (UV) B radiation, and to test for the development of photoprotection by subsequent irradiation with a single erythemal UVB dose. METHODS: A total of 26 healthy volunteers were divided into four groups: group 1 (n = 9) were given whole-body UVB irradiation for 10 consecutive days with 0.7 minimal erythema dose (MED), group 2 (n = 9) were irradiated as in group 1 followed 24 h later by a single UVB dose of 3 MED on buttock skin, group 3 (n = 4) were irradiated with a UVB dose of 3 MED on buttock skin, and group 4 (n = 4) were not irradiated. Skin biopsies were collected 24 h after the final irradiation and stained for cyclins A, B1, D1, and p16, p18, p21, p27, p53, pRB, Bax and Bcl-2. RESULTS: The expression of cyclin D1, p18 and p21 was significantly higher in groups 1 and 2 compared with the nonirradiated group 4 controls and, in group 2, the expression of pRB, p53 and Bax was also increased. In group 3, only p53 and Bax proteins were significantly elevated compared with group 4. The expression of cyclin D1, p16, p18, p27, pRB and Bcl-2 was higher in group 2 compared with group 3. CONCLUSIONS: Suberythemal UVB radiation was sufficient to cause changes in the expression of several epidermal cell cycle proteins. When tested by irradiation with a single erythemal UVB dose following the repeated exposures, no photoprotection against the UV-induced alteration in cell cycle protein expression was apparent.

Vitamin D3 deficiency enhances contact hypersensitivity in male but not in female mice.

To ascertain the influence of vitamin D3 and its metabolites on the function of the skin immune system and the induction of the contact hypersensitivity (CHS) response, a population of vitamin D3-deficient BALB/c mice was established, through dietary vitamin D3 restriction and limitation of exposure to UVB irradiation. Vitamin D3 normal female mice had higher CHS responses than their male counterparts, and dietary vitamin D3 deficiency significantly increased the CHS responses in male, but not in female, mice. This change in the vitamin D3-deficient male mice was not due to an alteration in skin dendritic cell function including antigen carriage, migration or costimulatory molecule expression. In addition, 18 h after sensitisation, the lymph node populations in the vitamin D3-deficient and normal male mice showed similar proliferation and IFN-gamma production. However, during the sensitisation phase of CHS, there was lower lymphocyte recruitment to the skin draining lymph nodes of the vitamin D3-deficient and normal male mice compared with their female counterparts which could account for the difference between the sexes in the extent of the CHS response. These results indicate the vitamin D system can influence cutaneous immune responses in male mice, but this did not occur through the modulation of the dendritic cell functions analysed.

Systematic administration of chloroquine in discoid lupus erythematosus reduces skin lesions via inhibition of angiogenesis.

BACKGROUND: Discoid lupus erythematosus (DLE) is a chronic cutaneous form of lupus erythematosus, characterized by inflammation and scarring skin lesions, with lymphocyte infiltration and vasodilation. Antimalarial drugs have beneficial therapeutic effects in DLE, partially resulting from their immunomodulating and photoprotective properties. The possible influence of these drugs on angiogenesis has not been previously evaluated. AIMS: To investigate the impact of chloroquine (CQ) treatment on the expression of vascular endothelial growth factor (VEGF, a major regulator of angiogenesis) and CD34 (a transmembrane glycoprotein expressed on endothelial cells and involved in tethering lymphocytes) in patients with DLE. METHODS: A 3-mm skin biopsy was taken from typical skin lesions in 10 people with DLE. Another biopsy was taken from the same area after 3 months of treatment with CQ (250 mg/day). Skin sections were stained with monoclonal antibodies directed against VEGF and CD34. The intensity of epidermal VEGF expression, and the number and area of CD34-positive dermal blood vessels were assessed. RESULTS: CQ treatment induced a reduction in epidermal VEGF expression. It also resulted in a significant decrease in the median number of CD34+ dermal blood vessels (from 219 to 125 vessels per mm(2)). Furthermore the median vessel area was significantly lowered from 9.76 x 10(6) to 6.92 x 10(6) mm(2) per mm(2) of the dermis. CONCLUSIONS: These results indicate that one beneficial effect of CQ treatment in DLE may be due to its antiangiogenic properties.

The effects on human health from stratospheric ozone depletion and its interactions with climate change.

Ozone depletion leads to an increase in the ultraviolet-B (UV-B) component (280-315 nm) of solar ultraviolet radiation (UVR) reaching the surface of the Earth with important consequences for human health. Solar UVR has many harmful and some beneficial effects on individuals and, in this review, information mainly published since the previous report in 2003 (F. R. de Gruijl, J. Longstreth, M. Norval, A. P. Cullen, H. Slaper, M. L. Kripke, Y. Takizawa and J. C. van der Leun, Photochem. Photobiol. Sci., 2003, 2, pp. 16-28) is discussed. The eye is exposed directly to sunlight and this can result in acute or long-term damage. Studying how UV-B interacts with the surface and internal structures of the eye has led to a further understanding of the location and pathogenesis of a number of ocular diseases, including pterygium and cataract. The skin is also exposed directly to solar UVR, and the development of skin cancer is the main adverse health outcome of excessive UVR exposure. Skin cancer is the most common form of malignancy amongst fair-skinned people, and its incidence has increased markedly in recent decades. Projections consistently indicate a further doubling in the next ten years. It is recognised that genetic factors in addition to those controlling pigment variation can modulate the response of an individual to UVR. Several of the genetic factors affecting susceptibility to the development of squamous cell carcinoma, basal cell carcinoma and melanoma have been identified. Exposure to solar UVR down-regulates immune responses, in the skin and systemically, by a combination of mechanisms including the generation of particularly potent subsets of T regulatory cells. Such immunosuppression is known to be a crucial factor in the generation of skin cancers. Apart from a detrimental effect on infections caused by some members of the herpesvirus and papillomavirus families, the impact of UV-induced immunosuppression on other microbial diseases and vaccination efficacy is not clear. One important beneficial effect of solar UV-B is its contribution to the cutaneous synthesis of vitamin D, recognised to be a crucial hormone for bone health and for other aspects of general health. There is accumulating evidence that UVR exposure, either directly or via stimulation of vitamin D production, has protective effects on the development of some autoimmune diseases, including multiple sclerosis and type 1 diabetes. Adequate vitamin D may also be protective for the development of several internal cancers and infections. Difficulties associated with balancing the positive effects of vitamin D with the negative effects of too much exposure to solar UV-B are considered. Various strategies that can be adopted by the individual to protect against excessive exposure of the eye or the skin to sunlight are suggested. Finally, possible interactions between ozone depletion and climate warming are outlined briefly, as well as how these might influence human behaviour with regard to sun exposure.

Repeated low-dose ultraviolet (UV) B exposures of humans induce limited photoprotection against the immune effects of erythemal UVB radiation.

BACKGROUND: Exposure of human subjects to ultraviolet (UV) B radiation causes immunosuppression. Most experiments to date have not tested the effects of low daily doses of UVB radiation. OBJECTIVES: To ascertain whether photoprotection against several UV-induced immune effects might develop following repeated exposure. METHODS: Groups of approximately 30 healthy individuals were given whole-body UVB irradiation on each of 10 consecutive days with 0.7 minimal erythema dose, or whole-body irradiation as before followed by a single erythemal UVB dose on a small body area, or irradiated only with a single erythemal UVB dose on a small body area, or were not irradiated. They were sensitized with diphenylcyclopropenone (DPCP) 24 h after the final dose, and skin biopsies collected to assess cytokine mRNA expression and the number of cells with thymine dimers and expression cyclooxygenase (COX)-1 and COX-2. RESULTS: The contact hypersensitivity (CHS) response to DPCP was significantly lower in the three irradiated groups compared with the unirradiated controls, while cutaneous interleukin (IL)-1beta, IL-6, IL-10 and tumour necrosis factor-alpha mRNAs, COX-1 and COX-2 and thymine dimers were all significantly higher. When the single erythemal UVB dose was given following the repeated low exposures, a slight downregulation in cytokine expression and thymine dimer formation was indicated. CONCLUSIONS: The repeated low doses of UVB protected to a limited extent against the effects of an erythemal UVB dose on cytokine expression and thymine dimer formation, but not on CHS or COX enzymes.

Circulating leukocyte and cytokine responses to measles and poliovirus vaccination in children after ultraviolet radiation exposures.

Suberythemal ultraviolet radiation (UVR) exposures of children are used routinely in Russia to prevent rickets and to strengthen general health. The aim of the present study was to re-evaluate the effects of such a regime on immune responses as UVR is now recognised to suppress cell-mediated immunity in many animal models. Seventeen infants were immunised with attenuated measles and recall polio vaccines of whom 10 had been given a course of prophylactic UV exposures before the vaccinations. All the infants in the study developed an acute infectious conjunctivitis one week prior to the vaccinations and were convalescent at the time of the vaccination. They were bled on the day of the vaccinations and at several times thereafter to assess leukocyte percentages and plasma cytokine levels. On the day of the vaccinations, an active immune response was apparent. The UV-exposed children differed from the unexposed children by having a smaller percentage of natural killer cells and a higher percentage of CD25-positive cells. In the days following the vaccinations, the UV-exposed infants had a lowered percentage of total lymphocytes with increased percentages of monocytes, eosinophils, neutrophils and HLA-DR-positive cells as well as higher concentrations of plasma IL-1beta and IL-10 compared with the unexposed infants. There were no local or systemic clinical reactions to the vaccines in the UV-group while a moderate rise in temperature of three children in the unexposed group occurred. Thus the UV irradiations modulated leukocyte percentages and plasma cytokine levels following the vaccinations, perhaps through the activation of a T helper 2-like response.

An influx of macrophages is the predominant local immune response in ovine pulmonary adenocarcinoma.

Infection with a retrovirus, Jaagsiekte sheep retrovirus (JSRV), causes ovine pulmonary adenocarcinoma (OPA). The excess production of surfactant proteins by alveolar tumour cells results in increased production of pulmonary fluid, which is characteristically expelled through the nostrils of affected sheep. The immune response to JSRV and the tumour is poorly understood: no JSRV-specific circulating antibodies or T cells have been detected to date. The aim of the present study was to obtain phenotypic evidence for a local immune response in OPA lungs. Specific-pathogen free lambs were infected intratracheally with JSRV. When clinical signs of OPA were apparent, the lungs were removed at necropsy and immunohistochemistry (IHC) was performed on lung sections using a panel of mouse anti-sheep mAbs. No influx of dendritic cells, B cells, CD4, CD8 or gammadelta T cells was seen in the neoplastic nodules or in their periphery. MHC Class II-positive cells were found intratumourally, peritumourally and in the surrounding alveolar lumina. In the tumours, many of these cells were shown to be fibroblasts and the remainder were likely to be mature macrophages. In the alveolar lumen, the MHC Class II-positive cells were CD14-positive and expressed high levels of IFN-gamma. They appeared to be immature monocytes or macrophages which then differentiated to become CD14-negative as they reached the periphery of the tumours. A high level of MHC Class I expression was detected on a range of cells in the OPA lungs but the tumour nodules themselves contained no MHC Class I-positive cells. On the basis of these findings, it is proposed that the lack of an effective immune response in OPA could result from a mechanism of peripheral tolerance in which the activity of the invading macrophages is suppressed by the local environment, possibly as a consequence of the inhibitory properties of the surfactant proteins.