Ceramides play major roles in maintaining the epidermal barrier. It has been sus-pected that the depletion of ceramides, associated with disrupted barrier function in the epidermis, leads to the clinical manifestation of dryness and inflammation seen in patients with psoriasis. The aim of the present study was to determine the relation-ship between the level of ceramide synthesis in the epidermis and the clinical severity in patients with psoriasis. Samples from lesional and unlesional epidermis obtained from psoriasis patients were incubated with [14C]serine, an initiator of ceramide syn-thesis. otal ceramide was fractionated using high performance thin layer chromato-graphy, and the radioactivity was measured. The clinical severity of psoriasis was graded according to the psoriasis area and severity index scoring system. The level of ceramide synthesis in the lesional epidermis of patients was significantly lower than that in the unlesional epidermis and bore a negative correlation with the clinical severity of psoriasis. The present results suggest that the decreased level of ceramide synthesis in the epidermis contributes to the clinical severity of psoriasis.

As dietary sources of gamma-linolenic acid [GLA; 18:3(n-6)], borage oil (BO; 24-25 g/100 g GLA) and evening primrose oil (PO; 8-10 g/100 g GLA) are efficacious in treating skin disorders. The triglycerol stereospecificity of these oils is distinct, with GLA being concentrated in the sn-2 position of BO and in the sn-3 position of PO. To determine whether the absolute level and/or the triglycerol stereospecificity of GLA in oils affect biological efficacy, epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut oil (HCO) diet for 8 wk. Subsequently, guinea pigs were fed diets of PO, BO or a mixture of BO and safflower oil (SO) for 2 wk. The mixture of BO and SO (BS) diet had a similar level of GLA as PO but with sn-2 stereospecificity. As controls, two groups were fed SO and HCO for 10 wk. Epidermal hyperproliferation was reversed by all three oils in the order of BO > BS > PO. However, proliferation scores of group PO were higher than of the normal control group, SO. The accumulations of dihomo-gamma-linolenic acid [DGLA; 20:3(n-6)], an elongase product of GLA, into phospholipids and ceramides, of 15-hydroxyeicosatrienoic acid (15-HETrE), the potent antiproliferative metabolite of DGLA, and of ceramides, the major lipid maintaining epidermal barrier, in the epidermis of group BO were greater than of groups BS and PO. Group BS had higher levels of DGLA, 15-HETrE and ceramides than group PO. With primary dependence on absolute levels, our data demonstrate that the antiproliferative efficacy of GLA in the epidermis is preferably exerted from sn-2 stereospecificity of GLA in BO.