retinol-acetate and Dermatitis--Contact

The adverse health effects caused by increased exposure to ultraviolet radiation (UVR) due to deterioration of stratospheric ozone are of major concern. These health effects include sunburn, skin cancer, cataracts and immune suppression. Immune suppression has been associated with the release of cytokines, a defect in antigen presentation, induction of suppressor T cells and suppression of contact hypersensitivity (CH). CH is typically assessed by the mouse ear swelling test (MEST). Previous studies have demonstrated enhanced CH responses with vitamin A acetate (VAA) dietary supplementation assessed by MEST and the local lymph node assay (LLNA). To determine the effect that VAA has on UVR-induced immune suppression, we examined both the induction and elicitation phases of CH using murine models. The MEST was used to evaluate the interaction of UVR and VAA on CH elicitation. However, a positive MEST response requires that the induction phase as well as the elicitation phase of CH be functional. The LLNA was used to evaluate the interaction of UVR and VAA only on CH induction. We tested the hypothesis that mice maintained on a VAA-enriched diet are more resistant to UVR-induced immune suppression (CH) than those maintained on a control diet. Mice were maintained on a VAA-enriched or the control diet for 3 weeks and then exposed to UVR 3 days prior to sensitization with 2,4-dinitrofluorobenzene (DNFB). VAA enhanced the MEST response in both UVR-exposed and non-UVR-exposed mice. The VAA-enriched diet did not significantly alter the LLNA response in either UVR- or non-UVR-exposed mice. However, there was significant suppression in CH by UVR as measured by the LLNA. These results indicate that (1) the VAA-enriched diet does not restore the number of proliferating cells in the CH induction phase of UVR-induced immunosuppression; (2) the immunosuppressive effects of UVR affect the induction phase of CH; and (3) the LLNA should be examined as an alternative to the MEST for measurement of UVR-induced immunosuppression. The data indicate that the VAA-enriched diet enhanced the elicitation response (MEST) but not the earlier induction phase (LLNA). Further studies are necessary to define mechanisms of action, but modulation of cytokines and effects of specific lymphocyte subsets, as well as systemic effects and local modulation at the site of elicitation are possible. Additionally, future studies to evaluate the effect of the VAA-enriched diet when multiple doses of

Topics: Animals; Dermatitis, Contact; Diterpenes; Female; Immune System; Mice; Mice, Inbred BALB C; Retinyl Esters; Ultraviolet Rays; Vitamin A

The contact sensitizing potential of various compounds was tested in mice maintained on a diet supplemented with vitamin A acetate. Substances were applied epicutaneously. After challenge, increases in ear thickness were measured and the differences in response between control and treated groups determined by the Mann Whitney test. A number of sensitizers, including Dowicil 200, cinnamaldehyde, hydroxycitronellal and Kathon CG gave positive sensitivity responses.

Topics: Allergens; Animals; Dermatitis, Contact; Diterpenes; Drug Synergism; Drug-Related Side Effects and Adverse Reactions; Female; Mice; Mice, Inbred BALB C; Pharmaceutical Preparations; Retinyl Esters; Vitamin A

Various methods have been used to enhance the ability of laboratory animals to develop contact sensitivity to so-called weak sensitizers. The present studies have examined whether diets supplemented with vitamin A acetate (VAA) could enhance induction and elicitation of contact sensitivity to oxazolone in the mouse. Application of 0.3% oxazolone to VAA-fed mice resulted in increased DNA synthesis in the draining lymph nodes and increased ear thickness after challenge, in comparison with mice on a stock (standard) diet. Moreover, VAA-fed (but not control) mice were sensitized to 0.03% oxazolone as shown by DNA synthesis, increased arrival of syngeneic 51Cr-labelled lymphocytes in the draining lymph nodes, and ear swelling after challenge. These findings demonstrate that vitamin A enhances delayed hypersensitivity responses, and point to a role for vitamin A in developing an animal model capable of detecting weak contact sensitizers after topical application.

Topics: Animal Feed; Animals; Cell Movement; Dermatitis, Contact; Diterpenes; DNA; Hypersensitivity, Delayed; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Oxazolone; Retinyl Esters; Skin; Stimulation, Chemical; Vitamin A