Faith M. Strickland

Inhibition of UV-induced immune suppression and interleukin-10 production by plant oligosaccharides and polysaccharides.

Abstract— Application of Aloe barbadensis poly/oligosaccharides to UV‐irradiated skin prevents photosuppression of delayed‐type hypersensitivity (DTH) responses in mice. We tested the hypothesis that these carbohydrates belong to a family of biologically active, plant‐derived polysaccharides that can regulate responses to injury in animal tissues. C3H mice were exposed to 5 kJ/m2 UVB from unfiltered FS40 sunlamps and treated with between 1 pg and 10 μg tamarind xyloglucans or control polysaccharides methylcellulose or dextran in saline. The mice were sensitized 3 days later with Candida albicans. Tamarind xylogiucans and purified Aloe poly/oligosaccharides prevented suppression of DTH responses in vivo and reduced the amount of interleukin (IL)‐IO observed in UV‐irradiated murine epidermis. Tamarind xyloglucans were immunoprotective at low picogram doses. In contrast, the control polysaccharides methylcellulose and dextran had no effect on immune suppression or cutaneous IL10 at any dose. Tamarind xyloglucans and Aloe poly/oligosaccharides also prevented suppression of immune responses to alloantigen in mice exposed to 30 kJ/m2 UVB radiation. To assess the effect of the carbohydrates on keratinocytes, murine Pam212 cells were exposed to 300 J/m2 UVB radiation and treated for 1 h with tamarind xyloglucans or Aloe poly/oligosaccharides. Treatment of keratinocytes with immunoprotective carbohydrates reduced IL‐10 production by approximately 50% compared with the cells treated with UV radiation alone and completely blocked suppressive activity of the culture supernatants in vivo. The tamarind xyloglucans also blocked UV‐activated phosphorylation of SAPK/JNK protein but had no effect on p38 phosphorylation. These results indicate that animals, like plants, may use carbohydrates to regulate responses to environmental stimuli.

Immune regulation by polysaccharides: implications for skin cancer.

UV radiation causes sunburn, premature aging of the skin and is the major environmental carcinogen for squamous cell and basal cell skin cancer in humans. Besides causing mutations in DNA, UV radiation contributes to carcinogenesis by suppressing immune responses to highly antigenic, newly arising neoplasms. Strategies aimed at preventing UV-induced immune suppression, the mechanism of action of the agents used, and the significance of immune protection for prevention of skin cancer are reviewed. This review focuses on the use of plant polysaccharides to prevent immune damage triggered by UV radiation, an approach that goes beyond absorption of UV radiation by sunscreens as a means of reducing tissue damage. The efficacy and mechanism of action of these agents in preserving T cell-mediated immunity to model antigens in human beings and in laboratory animals are discussed.

Induction of Primary Cutaneous Melanomas in C3H Mice by Combined Treatment with Ultraviolet Radiation, Ethanol and Aloe Emodin¶

Abstract The role of ultraviolet (UV) radiation in the induction of nonmelanoma skin cancer is widely accepted, although its precise contribution to the development of primary cutaneous melanoma skin cancer requires further definition. We found that painting aloe emodin, a trihydroxyanthraquinone from Aloe barbadensis, in ethyl alcohol vehicle on the skin of mice in conjunction with exposure to UVB (280–320 nm) radiation results in the development of melanin-containing skin tumors. C3H/HeN mice were treated thrice weekly with aloe emodin in a 25% ethanol in water vehicle and exposed to 15 kJ/m2 UV radiation. Neither ethanol vehicle nor aloe emodin alone induced skin tumors in the absence of UV radiation. In two separate experiments, 20–30% of the mice treated with a combination of UV radiation and ethanol vehicle and 50–67% of the UV-irradiated animals given aloe emodin in ethanol vehicle developed primary cutaneous melanin-containing tumors. The diagnosis of melanoma was established using Fontana silver stain for melanin; these tumors were negative for vimentin and keratin. Melanin-containing melanosomes were observed by transmission electron microscopy in tumors diagnosed as melanomas. Although the mechanism of carcinogenesis in these mice is currently unknown, our findings have led to the development of the first facile murine model for the induction of primary melanoma. This model has the potential to clarify the role of UV radiation in the etiology of malignant melanoma.

Three-Arm Randomized Phase III Trial: Quality Aloe and Placebo Cream Versus Powder as Skin Treatment During Breast Cancer Radiation Therapy

BACKGROUND The efficacy of aloe extract in reducing radiation-induced skin injury is controversial. The purpose of the present 3-arm randomized trial was to test the efficacy of quality-tested aloe extract in reducing the severity of radiation-induced skin injury and, secondarily, to examine the effect of a moist cream versus a dry powder skin care regimen. MATERIALS AND METHODS A total of 248 patients with breast cancer were randomized to powder, aloe cream, or placebo cream. Acute skin toxicity was scored weekly and after treatment at weeks 1, 2, and 4 using a modified 10-point Catterall scale. The patients scored their symptom severity using a 6-point Likert scale and kept an acute phase diary. RESULTS The aloe formulation did not reduce acute skin toxicity or symptom severity. Patients with a greater body mass index were more likely to develop acute skin toxicity. A similar pattern of increased skin reaction toxicity occurred with both study creams compared with the dry powder regimen. CONCLUSION No evidence was found to support prophylactic application of quality aloe extract or cream to improve the symptoms or reduce the skin reaction severity. Our results support a dry skin care regimen of powder during radiation therapy.

UVB irradiation decreases the magnitude of the Th1 response to hapten but does not increase the Th2 response.

Exposure of murine skin to low doses of ultraviolet‐B (UVB) radiation before sensitization with hapten reduces the ability of antigen presenting cells (APC) in the draining lymph nodes to initiate contact hypersensitivity responses in vivo and results in the induction of hapten‐specific suppressor T cells. In the present study, we tested the hypothesis that exposure of skin to UVB radiation suppresses T cell responses to hapten in vivo by altering the functions of APC, resulting in decreased stimulation of Th1 lymphocytes, which mediate contact hypersensitivity responses, and preferential activation of Th2 cells. C3H/HeN mice were exposed to either a single 2 kJ/m2 dose of UVB or to 400 J/m2 of UVB daily from FS40 sunlamps for four consecutive days and sensitized with fluorescein isothiocyanate on UV‐irradiated skin. Draining lymph node cells were collected 18 h after sensitization and co‐cultured with nylon wool‐purified T cells from naive or fluorescein‐immunized mice. Unseparated lymph node cells or sorter‐purified fluorescein‐bearing APC from UV‐irradiated mice induced less T cell proliferation than APC from non‐UV‐exposed mice. Lymph node cells produced less Th1 and Th2‐associated cytokines, interferon‐gamma and interleukin‐4, respectively, in response to APC from UV‐irradiated animals compared with APC from unirradiated, fluorescein‐sensitized mice. Thus, low doses of UV radiation do not result in preferential stimulation of Th2 response in lymph nodes, and results from cloned cell lines may incompletely reflect T cell responses in vivo.