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Cytokines and irritant contact dermatitis.

Skin irritation is a complex phenomenon that involves resident epidermal cells, fibroblasts of dermis, and endothelial cells as well as invading leukocytes interacting with each other under the control of a network of cytokines and lipid mediators. Keratinocytes play an important role in the initiation and perpetuation of skin inflammatory reactions through the release of, and responses to cytokines. While resting keratinocytes produce some cytokines constitutively, a variety of environmental stimuli, such as tumor promoters, ultraviolet light and chemical agents, can induce epidermal keratinocytes to release inflammatory cytokines (IL-1, TNF-alpha), chemotactic cytokines (IL-8, IP-10), growth promoting cytokines (IL-6, IL-7, IL-15, GM-CSF, TGF-alpha) and cytokines regulating humoral vs. cellular immunity (IL-10, IL-12, IL-18). The role of cytokines in xenobiotics-induced skin irritation and the early molecular events that follow the treatment with irritant compounds will be discussed.

Calcium↗

Allergenic alpha-methylene-gamma-butyrolactones. Stereospecific syntheses of (+)- and (-)-gamma-methyl-alpha-methylene-gamma-butyrolactones. A study of the specificity of (+) and (-) enantiomers in inducing allergic contact dermatitis.

The enantiomers of gamma-methyl-alpha-methylene-gamma-butyrolactone have been prepared stereospecifically from (R)- and (S)-glutamic acid. Three groups of guinea pigs have been sensitized (Feund complete adjuvant technique) to the (+) isomer, the (-) isomer, and the (+/-) mixture. The animals have been tested with each of the enantiomers and with a mixture of the compounds. Only the (-) enantiomer showed some specificity: guinea pigs sensitized to this enantiomer react weakly to the other compound; in turn, animals sensitized to the (+) enantiomer react similarly to both antipodes. Interestingly, reaction to the (+/-) mixture in each group of guinea pigs was the sum of skin responses to the individual enantiomer. These results should be contrasted with sensitization to (+)- and (-)-frullanolides, sesquiterpene lactones for which strong stereospecificity was observed.

4-Butyrolactone↗