Effects of lithium carbonate (Li2CO3) on in-vitro-cultured normal human skin explants

The early morphological changes induced by lithium carbonate, a well-known psoriasis-provoking drug, were studied on cultured skin. Normal human skin from patients undergoing mastectomy was cultured in the p resence of 3 mM, 6 mM and 10 mM of Li2CO3 for 4 days. The morphological cha nges were then evaluated by three observers in a blind manner and their rep orts were matched and collated. The cultured skin in the presence of Li2CO3 showed cell crowding of keratin ocytes in the lower part of the epidermis, indicating epidermal hyperplasia . Another striking finding was intercellular oedema and vacuolar alteration with formation of small cavities in the upper dermis. There was no evidenc e of parakeratosis or any other histological characteristic of psoriasis, e xcept hyperproliferation of the epidermis. Based on our knowledge of mechanisms of lithium action, we proposed two com petitive explanations for its action on the epidermis: i) that lithium acts directly on dividing cells of the epidermis; and ii) that it acts indirect ly by altering epidermal barrier function. Although we lack definite proof, we suggest that the observed morphological changes, in particular the non-specific stimulus to epidermal proliferatio n, ape the primary events which initiate the process that will ultimately l ead to the development of psoriatis in a predisposed patient.