Suppression of epidermal graft-versus-host disease with ultraviolet radiation.
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Animals↗
Biomedical subjects
W L Morison
Publications and source records attributed to W L Morison.
Systemic suppression of contact hypersensitivity by UVB radiation is unrelated to the UVB-induced alterations in the morphology and number of Langerhans cells.
Exposure of mice to UVB (280-320 nm) ultraviolet radiation reduces contact hypersensitivity (CHS) reactions to chemicals that are applied subsequently to unirradiated skin. It also decreases the number and alters the morphology of Langerhans cells at the site of irradiation. We addressed the question of whether the systemic suppression of CHS was related to these modifications of Langerhans cells by UVB radiation. In mice treated on the dorsum with UVB radiation, the number and morphology of Langerhans cells in the unexposed areas of skin used for inducing and eliciting CHS appeared normal. Therefore, the depression of CHS could not be attributed to a depletion of Langerhans cells at the sites of application of the sensitizing agent. We also examined the correlation between alterations in Langerhans cells and systemic suppression of CHS after treatment with various types of nonionizing radiation. Treatment of mice with UVA (320-400 nm) radiation eliminated detectable Langerhans cells from the exposed skin, based on ATPase staining and electron microscopy, but did not reduce CHS; in fact, CHS was enhanced in these animals. Neither rose bengal nor eosin, in combination with visible (greater than 400 nm) radiation, affected the number or appearance of Langerhans cells, even though microscopic evidence of phototoxicity was present. However, rose bengal plus visible radiation depressed CHS reactions that were induced and elicited through unexposed skin. Depletion of Langerhans cells from dorsal skin by exposure to UVA radiation did not prevent suppression of CHS by subsequent exposure of the Langerhans cell-depleted skin to UVB radiation. We conclude that systemic suppression of CHS by UVB irradiation is not related to the numerical and morphological alterations in Langerhans cells that occur locally at the site of irradiation.
Animals↗
Environmental UVA radiation and eye protection during PUVA therapy.
Experimental and clinical evidence suggests that patients receiving psoralens plus UVA radiation (PUVA) therapy for the treatment of psoriasis or other skin diseases run the risk of developing cataracts. The total exposure to UVA radiation of these patients has been difficult to quantify because they are exposed to UVA radiation in the environment as well as during PUVA therapy. In our studies, the spectral irradiances of possible environmental sources of UVA radiation (sunlight, daylight and cool white fluorescent bulbs, and incandescent bulbs) were measured and compared to the spectral irradiance of a bank of PUVA bulbs. Sunlight and PUVA bulbs were found to have similar irradiances in the UVA waveband. Window glass reduced the UVA irradiance from sunlight. Artificial sources of illumination had a very low UVA irradiance compared with PUVA bulbs and sunlight. These results indicate that patients should protect their eyes from sunlight both outdoors and indoors after ingestion of psoralens; however, protection from incandescent bulbs or cool white and daylight fluorescent bulbs is much less important, and possibly unnecessary.
Cataract↗
The role of UVB radiation in the induction and elicitation of photocontact hypersensitivity to TCSA in the mouse.
Photocontact hypersensitivity (PHS) to 3,3',4',5 tetrachlorosalicylanilide (TCSA) can be induced in mice by using cyclophosphamide as an immunopotentiator. Only UVA (320-400 nm) radiation was required for both sensitization and elicitation of PHS. The reaction was successfully transferred to syngeneic mice by injecting them with lymph node cells from sensitized donors, a finding that demonstrates the immunologic nature of PHS. The presence of UVB (280-320 nm) radiation was not necessary for sensitization and did not increase PHS beyond the levels observed with UVA radiation alone. Ultraviolet radiation in the UVB range (plus a small amount of UVA radiation) from FS40 sunlamps in the dose employed did not induce statistically significant PHS to TCSA, nor did it elicit a significant response in mice sensitized with TCSA plus UVA radiation. However, treatment of mice with UVB radiation at a distant site 6 days before sensitization suppressed the induction of PHS. This suppression appeared to be analogous to the systemic suppression of ordinary contact hypersensitivity in mice by UVB radiation.
Adjuvants, Immunologic↗
Systemic suppression of contact hypersensitivity in mice by psoralen plus UVA radiation (PUVA).
Treatment of mice with 8-methoxypsoralen plus longwave UV radiation (UVA, 320-400 nm) decreased their response to contact sensitizers applied subsequently to unirradiated skin. This decreased reactivity exhibited a delayed time course, it affected the afferent but not the efferent phase of the reaction, and it was associated with the development of splenic suppressor cells. These suppressor cells were antigen-specific T lymphocytes, and they prevented the induction, but not the elicitation, of contact hypersensitivity in recipient mice. In all of these characteristics, the decreased reactivity induced by treatment with psoralen plus UVA radiation (PUVA) resembled that produced by UV radiation of shorter wavelengths (less than 320 nm). These studies suggest that PUVA treatment may initiate the same sequence of cellular events as does exposure to sunlamp (UVB, 280-320 nm) radiation, leading to preferential activation of the suppressor cell pathway.
Animals↗
Abnormal lymphocyte function following long-term PUVA therapy for psoriasis.
The surface markers and function of peripheral blood lymphocytes were examined in patients on long-term therapy with methoxsalen and UV-A radiation (PUVA). Ten patients with psoriasis were selected because they had received a high exposure to PUVA therapy, i.e., more than 200 treatments over 2-6 years with cumulative exposure doses of 1700-6000 J/cm2 UV-A radiation. Results were compared to those obtained with lymphocytes from untreated patients and UV-B treated patients with psoriasis. The PUVA-treated patients had low levels of E rosette-forming cells in the peripheral blood and markedly impaired lymphocyte responses following stimulation with optimal and suboptimal doses of mitogens. The sensitivity of lymphocytes to in vitro treatment with PUVA was similar in the three groups of patients. The results of this study indicate that long-term PUVA therapy alters the function and cell-surface markers or distribution of lymphocytes.
Adolescent↗
The role of suppressor cells in the induction of murine photoallergic contact dermatitis and in its suppression by prior UVB irradiation.
Induction in mice of marked photoallergic contact dermatitis (PCD) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) with UVA (320 to 400 nm) radiation requires pretreatment with cyclophosphamide (CY). Attempts to induce photoallergic contact dermatitis without CY result in only a small degree of sensitivity, accompanied by significant net splenic suppressor cell activity. These suppressor cells are antigen specific, inhibit the induction but not the elicitation of photoallergic contact dermatitis to TCSA, and are T lymphocytes. Exposure of mice to UVB (280 to 320 nm) radiation at a site distant from that of sensitization, before CY administration and sensitization, inhibits the development of photoallergic contact dermatitis. This is analogous to the suppression of allergic contact dermatitis (ACD) observed in mice after exposure to UVB radiation; such suppression is accompanied by the formation of antigen-specific splenic suppressor cells. However, in contrast to the findings with allergic contact dermatitis, splenic suppressor cells are not detected in mice that are treated with UVB radiation before CY administration and sensitization to TCSA. This is presumably because CY prevents their formation. This provides evidence that UVB-irradiated mice have a second form of anergy that is not mediated by suppressor cells.
Animals↗
Combined methotrexate-PUVA therapy in the treatment of psoriasis.
Thirty patients with psoriasis were treated with a 3-week course of methotrexate followed by a combination of PUVA therapy and methotrexate. When lesions cleared to less than 1% UVA-exposed body involvement, the methotrexate was stopped and PUVA therapy alone was used as maintenance therapy. This protocol achieved clearance of disease in twenty-eight of the thirty patients in a mean of 5.7 (+/- 1.0) weeks, with 9.3 (+/- 3.0) exposures to PUVA therapy and a final UVA radiation dose at clearance of 6.2 (+/- 2.5) J/cm2. The mean total dose of methotrexate was 93.0 mg (range, 67.5-127.5 mg). The only significant adverse effect seen was prolonged phototoxicity in eight patients. By reducing the total cumulative exposure dose of PUVA therapy, this treatment may reduce long-term side effects.
Adult↗
Reduction of the fraction of circulating helper-inducer T cells identified by monoclonal antibodies in psoriatic patients treated with long-term psoralen/ultraviolet-A radiation (PUVA).
Ultraviolet radiation has been found to alter the distribution and function of human lymphocytes. To determine whether photochemotherapy (PUVA) alters circulating levels of T cell subset marker-bearing lymphocytes, cells from 9 patients with psoriasis undergoing PUVA therapy for several years (mean 4.6 +/- 1.4 yr), 17 patients with active untreated psoriasis, and 20 healthy volunteers were reacted with monoclonal antibodies to T cell surface markers, including OKT3 (all peripheral blood T cells), OKT4 (helper/inducer T cells), OKT6 (common thymocytes), and OKT8 (suppressor/cytotoxic T cells), and analyzed by flow cytometry. There were no differences in the distribution of T cell subsets between healthy volunteers and patients with active psoriasis. In contrast, the percentages of lymphocytes reacting with OKT3 and OKT4 were lower (by 16% and 12% percent respectively, p less than 0.0025) in the PUVA-treated patients compared to healthy volunteers or patients with active psoriasis that had not received PUVA therapy. There was no difference in the percentage of OKT8 and OKT6 bearing cells. Squamous cell carcinoma of the skin subsequently developed in 2 of 3 PUVA-treated patients with the lowest percentages of T4-bearing cells. These findings indicate that long-term PUVA therapy is associated with a reduction in circulating helper/inducer T cells. This reduction may have a role in the altered immune function reported in PUVA-treated patients.
Antibodies, Monoclonal↗
In vitro assay for phototoxic chemicals.
The photosensitizing potential of chemicals known to produce photosensitivity in humans was compared to chemicals not considered to be photosensitizers in an in vitro assay. The assay involved exposure of human lymphoid cells to UVA (320-400 nm), and in some cases UVB (280-320 nm) radiation, in the presence of the chemicals and the assessement of phototoxicity as measured by the incorporation of 3[H]-thymidine into nuclear DNA. All known photosensitizers tested were found to be phototoxic, while the nonphotosensitizing agents, with the exception of retinoic acid, were not phototoxic. Peripheral blood mononuclear cells were compared to a T lymphoblastoid cell line as target cells; the latter were superior in terms of convenience, cost and reproducibility of results. This test system has potential as a predictive assay for detecting additional phototoxic chemicals.
Cells, Cultured↗
UV-B phototherapy in the prophylaxis of polymorphous light eruption.
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Humans↗
Solar urticaria: treatment with PUVA and mediator inhibitors.
Several therapeutic regimes for solar urticaria were evaluated. A short course of PUVA therapy produced a marked increase in the minimal dose of radiation required to produce urticaria in the six patients treated. This objective evidence of improvement was supported by the patients' reports of greatly increased tolerance to sun-exposure. Chlorpheniramine, an antihistamine, produced a slight increase in the minimal dose of radiation necessary to produce urticaria but its effectiveness was limited by side-effects. Indomethacin, an inhibitor of prostaglandin synthetase, produced no beneficial effect.
Adolescent↗
Polymorphous light eruption: a common reaction uncommonly recognized.
Polymorphous light eruption (PMLE) is usually considered to be an uncommon complaint, although the prevalence in the general population has not been studied. In a survey of 271 apparently healthy subjects, 10% gave a history consistent with a diagnosis of PMLE. The clinical characteristics in the survey cases of PMLE were similar in most respects to those of patients presenting to a clinic with this disorder. However, there was one notable exception, in that there was a striking difference between the clinic and survey cases in the amount of sunlight required to trigger the eruption. Clinic patients required a mean exposure of 30 min as compared with over 3 h in the survey cases. These findings suggest that PMLE is a common disorder but that many individuals have a high threshold of response to sunlight exposure.
Adolescent↗
Induction and transplantation of murine skin cancers induced by methoxsalen plus ultraviolet (320-400 nm) radiation.
Properties of skin tumors resulting from treatment of mice with ip methoxsalen plus UVA (320-400 nm) radiation (PUVA) were compared to those of skin tumors induced by UVB (280-320 nm) radiation. Repeated treatment of C3H/HeN murine mammary tumor virus-negative (C3H-) mice with PUVA produced both fibrosarcomas and squamous carcinomas that were indistinguishable morphologically from UVB-induced tumors. Fragments of 12 primary PUVA-induced tumors were transplanted into normal and immunosuppressed syngeneic recipients, and all grew progressively. In contrast, 19 primary tumors induced by repeated exposure of C3H- mice to UVB grew only in the immunosuppressed mice and not in the normal recipients. The growth of graded doses of cells from 5 PUVA-induced tumors was compared in normal and UVB-irradiated recipients. No preferential growth in UVB-irradiated mice was observed, even though this is characteristic of UVB-induced tumors. Thus PUVA-induced tumors do not appear to have the same antigenic properties as UVB-induced tumors.
Animals↗
Differences in the immunologic reactivity of mice treated with UVB or methoxsalen plus UVA radiation.
Skin tumors induced in mice by chronic exposure to UVB radiation are often highly antigenic and regress when transplanted into normal syngeneic animals, but grow progressively in immunosuppressed mice. Exposure of mice to subtumorigenic doses of UVB radiation can abolish this immunologic rejection phenomenon. In this study, we have investigated the effects of treatment with 8-methoxypsoralen plus UVA radiation (PUVA) on the rejection of antigenic UVB-induced tumors. PUVA treatment, with either topical or systemic administration of the psoralen, did not alter the normal process of rejection of UVB-induced tumors. Mice treated with both minimally and markedly phototoxic doses of PUVA rejected tumors with a frequency similar to that seen in untreated animals, although these tumors grew progressively in UVB-irradiated mice. These results indicate that the effects of PUVA treatment differ from those of UVB irradiation in that PUVA treatment does not alter the immunologic rejection of UVB-induced tumors.
Animals↗
Influence of PUVA and UVB radiation on delayed hypersensitivity in the guinea pig.
Exposure of guinea pigs to UVA (320--400 nm) radiation following administration of 8-methoxypsoralen by gavage (referred to by the acronym, PUVA) or exposure to UVB (290--320 nm) radiation, produced suppression of the cutaneous delayed hypersensitivity reaction at the site of exposure to radiation and at distant nonexposed sites. In these experiments, the animals were immunized by injection of dinitrophenyl-bovine gamma-globulin (DNP-BGG) in complete Freund's adjuvant and delayed hypersensitivity responses were provoked by intradermal injections of DNP-BGG, DNP and BGG on the flanks. Exposure to erythemogenic doses of either PUVA or UVB radiation for 7 days prior to immunization and for the 7 days between immunization and challenge (total period of radiation: 14 days) produced inhibiton of responses to each of the test substances. In addition, treatment with erythemogenic doses of PUVA either for 7 days prior to immunization or during the interval between immunization and challenge with DNP-BGG, inhibited the delayed hypersensitivity responses at the site of irradiation and at a nonexposed site. These findings suggest that in vivo exposure to nonionizing radiation leads to both local and systemic alteration of certain immune responses.
Animals↗
The influence of ultraviolet radiation on allergic contact dermatitis in the guinea-pig. I. UVB radiation.
Guniea-pigs were sensitized by percutaneous application of dinitrochlorobenzene and exposed to UVB (280-320 nm) radiation. The exposure to radiation diminished the response to an elicitation dose of the hapten administered 14 days later within the site of irradiation. The exposure dose of radiation required to produce this effect resulted in a marked erythemal response, but this response did not conceal the contact allergic reaction. The site of elicitation of the allergic response had to be included in the exposure field.
Animals↗