Interferon-gamma is involved in photoimmunoprotection by UVA (320-400 nm) radiation in mice.
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Ultraviolet B radiation not only inflicts tumor-initiating DNA damage, but also impairs T cell-mediated immunity relevant to survival of the initiated cells. We have reported, however, that ultraviolet A radiation, in contrast, is immunologically innocuous in hairless mice and opossums, but renders the animals resistant to the immunosuppression by ultraviolet B, or its mediator cis-urocanic acid. Ultraviolet B irradiation of skin causes abundant release of numerous cytokines (interleukin-1, interleukin-6, interleukin-10, tumor necrosis factor-alpha); notably interleukin-12 and interferon-gamma do not appear to be upregulated. A recent report has indicated that interleukin-12 protects from photoimmunosuppression in mice, but it remains unclear whether interleukin-12 acts directly or via interferon-gamma, which it is known to stimulate. Here we investigate the possible role of interferon-gamma in UVA photoimmunoprotection, using interferon-gamma gene knockout mice in comparison with control C57/BL6 mice, and the systemic contact hypersensitivity reaction (induced by sensitization through a nonirradiated skin site) to measure immunity. interferon-gamma-/- mice raised normal contact hypersensitivity responses, and were unaffected, as were C57BL control mice, by ultraviolet A exposure. In response to ultraviolet B irradiation or topical cis-urocanic acid treatment, control mice became immunosuppressed by 69% and 27%, respectively, and interferon-gamma-/- mice by 79% and 27%. When ultraviolet B exposure or cis-urocanic acid was followed by ultraviolet A irradiation, however, contact hypersensitivity was totally restored in control mice, but remained suppressed by 55% and 25%, respectively, in interferon-gamma-/- mice. Injection of recombinant interferon-gamma in the interferon-gamma-/- mice restored the ultraviolet A protective effect against cis-urocanic acid-induced immunosuppression. These observations suggest that interferon-gamma plays a part in ultraviolet A immunoprotection from the suppressive effect of ultraviolet B radiation and, and that the mechanism appears to be via antagonism by this cytokine of the cis-urocanic acid immunosuppressive action. (+info)
Phytophotodermatitis associated with parsnip picking.
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Phytophotodermatitis to certain plant groups is a well recognised entity. The combination of sunlight exposure and contact with plants of the umbelliferae family leads to the development of painful, erythematous, and bullous lesions and later to cutaneous hyperpigmentation. Agricultural workers and many clinicians often fail to make this link when patients present with these lesions. An incident involving 11 patients is presented to high-light this problem. (+info)
Formation of antigenic quinolone photoadducts on Langerhans cells initiates photoallergy to systemically administered quinolone in mice.
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Quinolone antibacterial agents are well known to cause photoallergy as a side-effect. Murine photoallergy to fluoroquinolones is a T cell-mediated immune response, evoked either by systemic fluoroquinolone and subsequent exposure of skin to ultraviolet A light or by subcutaneous injection of fluoroquinolone-photomodified epidermal cells. In this photosensitivity, epidermal Langerhans cells may be photomodified initially with the drug and thus present photohaptenic moieties to sensitize and restimulate T cells. Although we have shown that Langerhans cells photocoupled in vitro with fluoroquinolones are capable of stimulating sensitized T cells, it remains unclear whether systemically given fluoroquinolone photomodifies Langerhans cells upon ultraviolet A irradiation of the skin and the Langerhans cells become photohapten-bearing, T cell-stimulatory cells. In a murine model of fleroxacin photoallergy induced by intraperitoneal injection of the drugs plus ultraviolet A irradiation of skin, we found that Langerhans cells as well as keratinocytes are photoderivatized with fleroxacin as demonstrated with a fluoroquinolone-specific monoclonal antibody. Langerhans-cell-enriched epidermal cells prepared from mice treated with fleroxacin and ultraviolet A induced proliferation of sensitized T cells, indicating that photomodified Langerhans cells are functional. There was an optimal range of ultraviolet A dose to quantitatively and qualitatively form fleroxacin-photomodified Langerhans cells, as excess ultraviolet A rather reduced the photoantigen-presenting capacity of Langerhans cells presumably because of drug phototoxicity. Our study suggests that Langerhans cells serve as photoantigen-presenting cells in drug photoallergy. (+info)
Quinolone-photoconjugated major histocompatibility complex class II-binding peptides with lysine are antigenic for T cells mediating murine quinolone photoallergy.
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Fluoroquinolone antibacterial agents cause photosensitivity dermatitis as an adverse effect and can function immunologically as photohapten. In a murine model of quinolone photoallergy, Langerhans cells are photomodified with a systemically given quinolone upon ultraviolet A irradiation of skin and thus present photohaptenic moieties to sensitize and restimulate T cells. The aim of this study is to determine the site of peptides/proteins photobound to quinolones and to assess the T cell antigenicity of quinolone-photocoupled peptides using Langerhans cells as photoadduct-presenting cells. On an amino acid composition analysis, lysine was preferentially degraded in bovine serum albumin that was ultraviolet A-conjugated with a representative quinolone ofloxacin. An affinity chromatographic study using a quinolone photoadduct-specific monoclonal antibody as ligand demonstrated preferential photocoupling of ofloxacin with a lysine-containing peptide. CD4+ T cells were purified from lymph nodes of BALB/c mice sensitized subcutaneously with ofloxacin-photomodified epidermal cells and from those sensitized epicutaneously via barrier-disrupted skin with a major histocompatibility complex class II (I-Ad)-binding, ofloxacin-photoconjugated peptide. These immune T cells proliferated in vitro in response to Langerhans cells loaded with class II-binding, lysine-containing peptides when photomodified with ofloxacin. Furthermore, epicutaneous application of the ofloxacin-photoconjugated peptide was able to prime mice for subsequent elicitation of photoallergy evoked with systemic ofloxacin and ultraviolet A light. This study suggests that lysine affords quinolone photocoupling of peptides and quinolone-photomodified peptides on class II molecules stimulate pathogenetic T cells in quinolone photoallergy. (+info)
Delayed reactivation of haloperidol induced photosensitive dermatitis by methotrexate.
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A man whose psoriasis was well controlled on methotrexate treatment developed pellagra-like photosensitive dermatitis when he started taking haloperidol. Reactivation of his dermatitis was observed with methotrexate as a recall photosensitivity phenomenon. This false photosensitivity reaction of methotrexate is an important but rarely encountered adverse effect. A possible interaction between methotrexate and haloperidol is emphasised. (+info)
Ultraviolet radiation causes less immunosuppression in patients with polymorphic light eruption than in controls.
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It is hypothesized that polymorphic light eruption is characterized by a partial failure of ultraviolet radiation-induced immunosuppression, resulting in a delayed-type hypersensitivity response to photo-induced antigens. We aimed to study the susceptibility of PLE patients to UVR-induced immunosuppression, by measuring the strength of sensitization to 2,4-dinitrochlorobenzene after UVR exposure, and to diphenylcyclopropenone without UVR exposure, in subjects with PLE and controls. Thirteen PLE patients and 11 controls were exposed to 1 minimum erythema dose (MED) of UVR delivered from Waldmann UV-6 bulbs to the upper inner arm. Twenty-four hours later at the same site they were exposed to a sensitizing dose of 2,4-dinitrochlorobenzene. One week later they were exposed to a sensitizing dose of diphenylcyclopropenone at a nonirradiated site. Three weeks later all subjects were challenged with four doses of 2,4-dinitrochlorobenzene and four doses of diphenylcyclopropenone. The resulting increase in skin thickness was measured with Harpenden callipers and summed over the four doses, to give a single value representing the reactivity of the subject to 2,4-dinitrochlorobenzene (Sigma DN) and diphenylcyclopropenone (Sigma DP). Among all subjects, there was a very strong correlation between Sigma DN and Sigma DP (Pearson correlation 0.56, p=0.004). The strength of the reaction to 2,4-dinitrochlorobenzene relative to the reaction to diphenylcyclopropenone was significantly greater among PLE patients than controls (p=0.04 independent samples t test of Sigma DP-Sigma DN). We conclude that induction of sensitization by 2,4-dinitrochlorobenzene is suppressed less by UVR in patients with PLE than in healthy controls. (+info)
Ultraviolet-radiation-induced erythema and suppression of contact hypersensitivity responses in patients with polymorphic light eruption.
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Ultraviolet-radiation suppresses cell-mediated immunity in healthy humans. It has been postulated that, in the short term, this immunosuppression prevents autoimmune responses to ultraviolet-radiation damaged skin. Patients with polymorphic light eruption (PLE) demonstrate abnormal responses to ultraviolet-radiation suggestive of an immune response to an ultraviolet-radiation-induced antigen. We investigated whether PLE patients (n=22) were resistant to ultraviolet-radiation-induced immunosuppression compared to skin-type, aged-matched controls (n=23). Groups of patients and controls (six subjects per group) received a single dose of solar-simulated ultraviolet-radiation of either 0, 0.6, 1 or 2 minimal erythema doses (MED). Erythema was quantified using a reflectance meter and all volunteers were sensitised on the irradiated site with dinitrochlorobenzene. Contact hypersensitivity responses (CHS) to dinitrochlorobenzene were quantified after challenge using ultrasound. Ultraviolet-radiation-induced erythema was comparable in patients and controls. CHS was comparable in unirradiated patients and controls. UVR-induced a dose-dependent suppression of CHS in all volunteers but patients were more resistant to immunosuppression after 1MED. Exposure to 1MED suppressed CHS by 78% in controls but induced less suppression in patients (44%, p < 0.01). Our data suggest that PLE patients have a flaw in their immunoregulatory response to ultraviolet-radiation it is only apparent over a narrow dose range around 1 MED. (+info)
The effect of solar-simulated radiation on the elicitation phase of contact hypersensitivity does not differ between controls and patients with polymorphic light eruption.
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It has been suggested that polymorphic light eruption (PLE) is characterized by a failure of ultraviolet radiation (UVR)-induced immunosuppression, resulting in a type-IV hypersensitivity response to photoinduced antigens. We measured the effect of solar-simulated radiation (SSR) on the elicitation phase of contact hypersensitivity to 2,4-dinitrochlorobenzene (DNCB), in ten PLE patients and 11 controls. Subjects were given a sensitizing dose of DNCB, and 3 wk later were exposed to 0.75 and 2 minimum erythema doses (MED) of SSR on the upper inner arm. Immediately and 24 h later these sites, and a non-irradiated control site, were challenged with DNCB. The resulting increase in skin thickness was measured with high-frequency ultrasound. Overall, 2 MED caused 17%-20% suppression of elicitation responses (compared with 93% suppression of sensitization reported previously), but the effect of SSR varied greatly between subjects, with some subjects showing potentiated responses, which may be of relevance to false-positive reactions in photopatch testing. In a repeated measures general linear model, SSR overall caused significant suppression of responses (p<0.001); there was less suppression in older subjects (p=0.009) but there was no significant difference between PLE patients and age-matched normal controls. These results contrast with our previous finding of a resistance to UVR-induced suppression of sensitization to DNCB in PLE. This difference may reflect the greater importance of Langerhans cells in the sensitization phase, and is consistent with the hypothesis that PLE arises from impaired suppression of Langerhans cell activation or migration. (+info)