THE EFFECT OF CHRONIC TREATMENT OF MICE WITH UROCANIC ACID ISOMERS

Trans-urocanic acid (trans-UCA) accumulates in the upper layers of the epidermis and can be isomerized to cis-UCA by UV light irradiation, C is-urocanic acid possesses immunosuppressive properties that have led to its consideration as one of the initiators of UV-induced immunosupp ression, High quantities of cis-UCA persist in human skin for prolonge d periods in the summer months, In the present study, mice were inject ed intradermally with trans-UCA and cis-UCA three times a week for 4 w eeks in order to ascertain the long-term effects of the presence of th ese compounds in the skin, The weight of mice and of their spleens wer e unaffected by the cis- or trans-UCA treatment, A decrease in thymus weight, accompanied by an increase in lymph node weight, was detected in the cis-UCA-treated mice compared with trans-UCA-treated mice and u ntreated controls, A net accumulation of lymphocytes and dendritic cel ls (DC) in lymph nodes was evident following cis-UCA treatment but the percentage of both CD4(+) and CD8(+) lymphocytes as well as Ia(+) DC remained constant among the different treatment groups, indicating tha t there was no specific migration of proliferation of a particular sub set of cells, The in vitro lymphoproliferative response of lymph node cells to the mitogen concanavalin A was significantly sup pressed by c is-UCA treatment, The density of Langerhans cells in the epidermis of the ears was not altered by the chronic cis-UCA treatment. However, ch ronic cis-UCA treatment did suppress the mixed skin lymphocyte reactio n response utilizing epidermal cells from the ears (an uninjected area of skin), indicating a systemic suppression, Compared with trans-UCA treatment, chronic cis-UCA treatment did not cause a significant reduc tion in the contact hypersensitivity response to oxazolone or the dela yed hypersensitivity response to herpes simplex virus, Thus, chronic t reatment with cis-UCA led to the suppression of some, but not all, of the immune parameters that are affected by UVB irradiation.