256 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS ANTIOXIDANTS, AGING SKIN, UV, FATTY ACIDS Antioxidants (e.g., BHA, BHT) can play a role in altering immune responses. They can alter CH responses and, when applied topically to experimental animals, alter the den- sity of epidermal immune macrophages such as LC and T-cells. The alterations may be metabolized via the arachidonic acid (AA)-prostaglandin pathway. BHA has immuno- suppressant activity at levels that are not cytotoxic, affecting both B- and T-cell func- tion. In addition, LCs are subject to free radical attack, and their numbers are decreased via lipid peroxidation, probably through mediation via AA or its metabolites. Quenching of the free radical oxygen molecules in this pathway by antioxidants irre- versibly inhibits the cyclooxygenase enzyme, thereby affecting AA metabolism directly and/or indirectly via oxidation of AA into its products, prostaglandin, and leukotrienes (9,17). In aging skin, not only is there a decrease in ETAF and T-cells, but also in LC respon- sible for recognition of foreign antigens. There is an age-associated decrease in delayed hypersensitivity in human skin. The decrease reflects, in part, the decrease in total number of circulating thymus-derived lymphocytes (T-cells) and in their responsiveness to standard mitogens (mitotic-producing agents). In addition, epidermal LC, the cell population believed to be responsible for recognition of foreign antigens, have been reported to decline during adulthood in sun-exposed sites, with further loss in habitu- ally sun-exposed skin of older people. This exaggeration of age-associated cell loss in habitually sun-exposed skin may be relevant to photocarcinogenesis in the elderly. The loss of LC would be expected to impair the skin's cell-mediated immune response, particularly contact sensitization, because these cells are necessary for processing foreign antigens. It seems likely that there is the induction of some biochemical transducer in the skin that converts the physical stimulus, i.e., ultraviolet light, into a biochemical signal (18). Studies have documented the presence of prostaglandin synthetase and active synthesis of prostaglandins in the skin of various animal species. Various stimuli, such as me- chanical trauma and physical injury, including UVB irradiation, activate phospholipase A2 and the oxidation of arachidonic acid (AA) to prostaglandins. There is increasing evidence to implicate prostaglandins (PGs), leukotrienes (LTs), and other related lipids in the regulation of immune cells. AA has a biphasic effect on the number and functions of LC. Low topical doses of AA increased LCs. Higher doses (2%) decreased LCs and suppressed skin immune reactions in animal models. The increase may be correlated with increased immune reactivity and the decrease with a suppressed immune response (19). Oleic acid and linoleic acid (LA) were tested. Linoleic acid, but not oleic acid, can be converted by cells into arachidonic acid. Oleic acid caused a modest depletion of LC. Linoleic acid caused a much greater depletion, comparable to the effects observed with AA. All three acids caused hyperplasia (increase in number of cells) of the keratinocytes. AA and LA caused an increase in the number of mice epidermal pigment cells, and both induced melanogenesis (20). As previously noted, UV light and AA alter the cutaneous immune response, possibly by production of prostaglandins (PG). Of the PGs, only PGE2 suppressed the response of the skin to contact allergens. This suggests a specific role for PGE2 in the skin immune response. It is also possible that PGE2 affects epi-

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