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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 D3 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 mm2). Furthermore the median vessel area was significantly lowered from 9.76 × 106 to 6.92 × 106 mm2 per mm2 of the dermis. Conclusions. These results indicate that one beneficial effect of CQ treatment in DLE may be due to its antiangiogenic properties. [ABSTRACT FROM AUTHOR]

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)-1 β, IL-6, IL-10 and tumour necrosis factor- α 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. [ABSTRACT FROM AUTHOR]

SUMMARY Varicella zoster virus (VZV) causes varicella (chickenpox) as the primary infection and zoster (shingles) on reactivation from latency, often many years later. One of the most common and most severe sequela of zoster is postherpetic neuralgia (PHN). Apart from age, factors which predispose towards PHN are unknown. In the present study, the concentration of a variety of Th1 and Th2 cytokines in the serum of 30 zoster patients at the time of the acute disease were correlated with the subsequent development of PHN in nine of these patients, but no association was found. In addition, although some cytokines such as IFN-γ , IL-6 and IL-8 were slightly raised in the zoster group compared with a group of normal healthy subjects of a similar age distribution, these differences only verged on significance. Antibody titres to VZV were raised in the zoster group compared with the controls but these did not differ between the patients who developed PHN and those who did not. Biopsies of zoster lesions were collected from nine patients. There were significantly fewer infiltrating lymphocytes in the lesions of the three patients who subsequently developed PHN compared with the six who did not, although the expression of the neuropeptide, substance P, did not differ between the two groups. It is possible that the poor inflammatory response at the time of the acute zoster may result in less effective containment of the VZV and more damage in the dermatome, thus contributing to the persistence of the neuralgia. [ABSTRACT FROM AUTHOR]

Background Cis -urocanic acid (cis -UCA), formed from the naturally occurring trans -isomer in the epidermis on ultraviolet (UV) radiation, initiates some of the changes leading to UV-induced immunosuppression, but its role in cutaneous carcinogenesis has not been fully investigated. Objectives To measure the concentration of UCA isomers in the photoexposed and non-photoexposed skin of patients with multiple non-melanoma skin cancer (NMSC), enrolled in different periods of the year, in comparison with control subjects. Patients/methods UCA isomers were determined by high-performance liquid chromatography analysis in samples from the outer arm (photoexposed site) and buttock (non-photoexposed site) obtained from 20 patients and 19 controls during the winter period (October to April), and from five patients and 11 controls during the summer period (June to September). Results In the winter months, no difference was found between patients and controls in the concentration of UCA or the percentage of cis -UCA in either site. In the summer months, the percentage of cis -UCA in the buttock of patients and controls was similar but it was significantly higher in the arm of the controls (42%) than in the patients (17%). Conclusions We conclude that different behaviour regarding sun exposure is the most likely explanation for these results, and that the concentration of UCA and its isomers does not reflect a tendency for individuals to develop NMSC. [ABSTRACT FROM AUTHOR]

Background Following the primary infection of the orofacial region with herpes simplex virus (HSV) type 1, the virus remains latent in the ganglia for the lifetime of the host but can reactivate at intervals and cause recrudescent lesions. The frequency of these episodes varies considerably from one individual to another. Objectives To compare immune responses in two groups of subjects: those with frequent orofacial lesions, defined as 10 or more per year (n = 12), and those with infrequent lesions, defined as three or fewer per year (n = 20). Methods Plasma and peripheral blood mononuclear cells were collected from each individual for the series of immunological tests listed in the following results section. Results Although IgG titres specific for HSV, measured by enzyme-linked immunosorbent assay (ELISA), were not different between the two groups, there was a significantly higher HSV-specific IgE titre in the frequent group. The percentages of CD3-, CD4- and CD8-positive cells in peripheral blood, assessed by flow cytometry, and the in vitro lymphoproliferative response to the non-specific mitogen concanavalin A, did not differ between the two groups. T-cell responses to HSV were assessed by in vitro lymphoproliferation with tritiated thymidine incorporation and subsequent calculation of the stimulation index; cytokine production [interferon (IFN)-γ and interleukin (IL)-10] into the culture supernatant as a result of the stimulation was measured by ELISAs. The mean ± SEM stimulation index was 4·1 ± 0·2 in the subjects with frequent lesions and 11·8 ± 3·1 in the subjects with infrequent lesions, a difference that was significant. The mean IL-10 concentrations found in the subjects with frequent and infrequent lesions were 154 and 110 pg mL-1, respectively, a difference that did not reach significance. However, the IFN-γ production was significantly lower in the subjects with frequent lesions compared with... [ABSTRACT FROM AUTHOR]

Sixty-five patients with recrudescent orofacial herpes simplex virus (HSV) infections all had circulating HSV-specific antibody measured by ELISA and cell-mediated immunity (CMI) to HSV by in vitro lymphoproliferation. Thirteen control subjects with no history of HSV were negative for both tests. Thirty-three patients, repeatedly investigated during 6 to 38 months, had between 1 and 8 recrudescences each. Lymphoproliferative responses to HSV were low during recrudescence, rose to a peak a few weeks later and then declined to a positive background level. However. ELISA titres and lymphoproliferative responses to concanavalin A were high throughout, and peripheral blood mononuclear cell (PBMC) subset numbers measured by fluorescent flow cytometry remained within normal limits. During HSV lesions, depressed lymphoproliferation lo HSV was abrogated by removal of CD8+ T cells from PBMC either by using a panning technique (nine patients) or by cell sorting (three patients). Reconstitution of the CD8-depleted population suppressed the lymphoproliferative response to HSV. Depletion of CD8+ T cells did not affect iymphoprolifcration to HSV out with recrudescence (four patients), nor lymphoproliferative responses to another antigen (PPD; five patients) during recrudescence. Thus, reduced lymphoproliferation to HSV during recrudescence may be due to HSV-specific CD8+ suppressor T lymphocyte function, rather than lack of HSV-responsive lymphocytes. This may result in depression of normal CMI responses to the virus during an asymptomatic recurrence allowing recrudescent lesions to develop. [ABSTRACT FROM AUTHOR]

The ability of epidermal antigen presenting cells (APC) to induce immune responses to herpes simplex virus (HSV) has been studied in mice of differing ages. Using an in vivo model of HSV infection we have demonstrated that neonatal epidermal cells (EC) induce specific suppression of DH to HSV in normal syngeneic adult mice. The suppression is transferable and mediated by T cells of the Lyt1+, Lyt2-, L3T4+ phenotype. The ability of EC to induce suppression persists up to 4 weeks of age, whereas EC from mice 6 weeks of age or older induce positive DH responses to the virus. This correlates with the susceptibility of mice of the different ages to HSV infection and their ability to mount DH responses to the virus. [ABSTRACT FROM AUTHOR]

This article discusses about mucocutaneous infections with herpes simplex virus (HSV) and their management. There are six known members of the family Herpsviridae which infect men: HSV-1 and HSV-2, varicella zoster virus, cytomegalo virus, Epstein Barr virus and human herpesvirus 6. They are classified as herpes virus. HSV belongs to the Alpha subfamily of herpesviruses and contains at least 33 proteins. Eight of these are associated with the envelop surface and are glycosylated. The genome has 152000 base pairs with potential to code for about 70 polypeptides. In-vitro HSV infects a variety of cells from several species and is generally cytopathic with a short replication cycle and rapid spread. During natural infection, HSV-1 has a predilection for the oral mucosa and HSV-2 for genital mucosa. Mucocutaneous HSV infections follow a typical clinical course in most individuals. HSV is confined almost ex

Urocanic acid (UCA) is found in the stratum corneum as the trans-isomer and, on ultraviolet (UV) irradiation, photoisomerization into cis-UCA takes place. Cis-UCA has been suggested to play a part in UV-induced immunosuppression. In the present study, the concentration of UCA and the percentage as cis-UCA at 10 different body sites of 20 normal volunteers were analysed. A large interindividual variation in total UCA concentration was found, but the mean UCA concentration in each site was similar, other than at the sole of the foot. There was little variation in the UCA content between sites normally exposed, and not exposed, to light, but the percentage of UCA in the cis form was clearly higher at exposed areas. [ABSTRACT FROM AUTHOR]

Exposure to ultraviolet radiation is associated with the development of cutaneous carcinomas, and with suppression of immune responses to a variety of antigens, including those of fungal, bacterial and parasitic origin, and contact sensitizers. UV irradiation also influences viral infections. It can affect viral mutation, the photolocalization of viral exanthems, viral oncogenesis, activation of viral genomes, and the suppression of immune responses to viruses. The evidence for, and mechanisms involved in, each of these categories is presented, and the effect of UV radiation on the virus-host interaction, particularly during persistent infections, is discussed. [ABSTRACT FROM AUTHOR]

Orf is a disease of sheep and goats which is caused by a parapox virus. It can be transmitted to humans, and is considered an occupational hazard by those handling sheep. In this paper we present the first report of both cell-mediated and humoral immune responses to naturally acquired orf virus infection in bumans. Lymphoproliferative responses of peripheral blood mononuclear cells of patients to an orf virus antigen were vigorous soon after infection, but rapidly declined. Orf virus antibody levels, detected by ELISA. were shown to rise during infection. Western blot analysis confirmed this, and demonstrated that the antibody produced in response to tbe infection was directed against the 40-kDa viral surface tubule protein. Where direct comparisons were possible, the immune response of bumans to orf virus infection was similar to that previously reported for sheep. Evidence was obtained suggesting that prior exposure to vaccinia virus (smallpox vaccination) provided no protection from subsequent orf virus infection. In addition, orf virus infection did not enhance immune responses to vaccinia virus antigens. [ABSTRACT FROM AUTHOR]

Ultraviolet radiation (UVR) is known to suppress some cell-mediated immune responses to antigens encountered during or soon after exposure. Phototherapy is widely used in psoriasis, and this study was undertaken to monitor changes in a range of immunological parameters during standard courses of treatment, with the aim of ascertaining whether such modulations contribute to the effectiveness of therapy. The responses of 17 patients with psoriasis undergoing UVB therapy, and four receiving PUVA therapy, were compared with 1 5 patients receiving coal tar treatment and four normal subjects undergoing UVB irradiation. In each case, samples were taken before starting therapy, after 4 weeks of therapy, and 4 weeks after completion of treatment. Serum immunoglobulin isotypes and complement components were within normal ranges in most of the psoriasis patients, and remained unchanged throughout therapy. Similarly, percentages of subsets of peripheral blood mononuclear cells (PBMC) were normal, and were unaltered by treatment. Patients who were already infected with herpes simplex virus (HSV), as demonstrated by a positive lymphoproliferation test in vitro, were monitored for asymptomatic HSV shedding and HSV recrudescences during therapy. There was little evidence that phototherapy caused reactivation ofthe virus. No significant alteration in lymphoproliferative response to HSV and to the mitogen concanavalin A was observed during therapy. Epidermal cells and blood adherent cells were used to present HSV to PBMC, depleted of adherent cells and enriched for T cells, in a lymphoproliferative assay. The functional antigen-presenting ability of adherent cells remained unchanged throughout therapy, whereas that of epidermal cells was suppressed during UVB irradiation and recovered, in most instances, after IIVB therapy had been completed. The epidermis of patients with psoriasis contained about three times the quantity of urocanic acid (UCA) of normal subjects, whereas the UCA concentration in suction blister fluid did not differ between the two groups. During UVB irradiation, the percentage of cis-UCA rose in both the epidermis and suction blister fluid of all subjects, and it remained elevated in the blister fluid alter therapy had finished. Tumour necrosis factor-a was measured in suction blister fluid, and its concentration did not alter consistently as a result of therapy. Whether any of the immunological parameters measured, and the changes noted, contribute to the effectiveness of phototherapy in the treatment of psoriasis remains uncertain. [ABSTRACT FROM AUTHOR]

In vitro lymphoproliferative responses of peripheral blood mononuclear cells (PBMC) from patients with cutaneous warts, caused by infection with human papillomavirus type 1 (HPV-1) or type 2 (HPV-2), were assayed during the course of treatment. Purified HPV-1 and HPV-2 were used as antigens, as well as herpes simplex virus (HSV) and concanavalin A (Con A). All patients had normal percentages of subsets within the PBMC population and normal lymphoproliferative responses to Con A. and those with a clinical history of HSV infections had positive lymphoproliferative responses to HSV. Responses to both HPV antigens were poor. Only 10 of 100 assays of PBMC from 26 patients showed a stimulation index greater than 2. Addition of interleukin 2 made little difference in most cases. No correlation of clinical status of warts. i.e. Improving, unchanged or resolved, with lymphoproliferation was found. When the PBMC were depleted of plastic-adherent cells and enriched for T cells, some samples which had not shown a lymphoproliferative response to HPV-1 or HPV-2 became positive; this response was abolished when the adherent cells were re-added. Thus it is possible that the adherent cell population from a proportion of patients contains cells which suppress lymphoproliferation, or that an immunoregulatory network is present so that Iymphoproliferation does not take place in vitro without prior activation and cloning of T cells. [ABSTRACT FROM AUTHOR]

Recovery from epidermal herpes simplex virus (HSV) infection depends primarily on development of an effective cell-mediated immune response, possibly generated following antigen (Ag) presentation by epidermal cells (EC). The ability of EC to present HSV Ag was investigated in i2 subjects with occasional recrudescent facial HSV infections. All had circulating HSV specific antibodies and cell-mediated immunity to the virus. Peripheral blood mononuclear cell suspensions, depleted of antigen presenting cells (APC) by glass adherence and then enriched for T cells by adsorption on nylon wool columns, did not proliferate in response to HSV Ag. Both EC suspensions, prepared from suction blister roofs, and glass-adherent peripheral blood mononuclear cells (AC) preincubated with ultraviolet-inactivated HSV, reconstituted the T-cell proliferative response to HSV. EC were more efficient than AC at presenting HSV Ag to T cells. Depletion of CD1+ cells from EC suspensions by cell sorting reduced their ability to present HSV Ag and augmentation of CD1+ cell numbers supplemented it. Preincubation of EC or AC with monoclonal antibodies to major histocompatibility complex class 11 antigens DP, DQ or DR, blocked the lymphoproliferative response to HSV Ag. Evidence was obtained that cells co-ordinately expressing products of the DP, DQ and DR loci are involved in presentation of HSV Ag by both EC and AC. [ABSTRACT FROM AUTHOR]

The immune response to herpes simplex virus (HSV) was studied in 59 patients with primary and recrudescent facial HSV infections. The patients included nine with atopic eczema, seven of whom had eczema herpeticum (EH). All patients had antibodies to HSV (measured by ELISA) and all but three had HSV-specific cell mediated immunity (CMI) (measured by in vitro lymphoproliferation). Thirteen control subjects were negative for both tests. All three patients with absent CMI to HSV had suffered from severe EH and had depressed CMI to HSV for several months following an attack. In two of these EH patients, a positive CMI response was produced by in vitro removal of CD8 + ve T lymphocytes from peripheral blood mononuclear cells using a panning technique. Thus the absence of CMI to HSV in these patients was due to suppressor cell function rather than a lack of specifically responsive cells. The other four EH patients with normal CMI to HSV had suffered less severe EH, but no association between the absence of CMI to HSV and serum IgE level or activity of the eczema was apparent in the atopic patients. No specific anti-HSV IgE antibody was detectable. [ABSTRACT FROM AUTHOR]

This article presents information about the research paper entitled "Patients with eczema herpeticum have prolonged depression of cell-mediated immunity to herpes simplex virus," presented by J. P. Vestey, S. E. M. Howie, M. Norval and J. P. Maingay at the British Society for Investigative Dermatology Annual Meeting, Cambridge, September 1987. A survey of 58 patients with primary and recrudescent facial herpes simplex virus lesions was undertaken to study the immune response to the virus. Nine patients with atopic eczema and 7 with eczema herpeticum were included.