ARE DISTURBANCES OF OMEGA-6-FATTY ACID METABOLISM INVOLVED IN THE PATHOGENESIS OF ATOPIC-DERMATITIS

Abstract

Recent evidence indicates that the primary defect in atopic dermatitis (AD) might concern the maturation and differentiation of T cells which infiltrate the skin or are unable to control T cell infiltration of the skin. Unfortunately, there is no information on thymus hormones, T cell differentiation factors or cytokines during early T cell maturation in atopic infants. One of these factors at fault might involve a deficiency of essential long-chain omega-6-fatty acids and E-type prostaglandins which are important for thymic T cell maturation and thymus hormone action. Deficiencies of 6-desaturated omega-6-fatty acids have been observed in plasma phospholipids, epidermal and red cell phospholipids of patients with AD, in umbilical cord plasma lecithin of newborn infants with increased cord blood IgE levels, in cord blood T-cells of `atopy-at-risk' newborn infants, in atopic monocytes, in adipose tissue lipids of patients with AD, in breast milk lipids of mothers with a history of AD, and in breast milk lipids of mothers of infants with AD. Reduced release of arachidonic acid has been measured in atopic monocytes and platelets. Diminished formation of prostaglandin E2 (PGE2) has been observed in atopic monocytes under stimulated and unstimulated conditions and in inflamed and non-inflamed atopic epidermis. PGE2 is able to suppress interleukin 4-induced IgE synthesis of human non-atopic mononuclear cells in vitro. We have demonstrated a suppressive effect of PGE1 and PGE2 on in vitro IgE synthesis of mononuclear blood cells of patients with AD and respiratory allergies. The T-cell differentiating effect of thymus hormones is associated with a high release of E-type prostaglandins, and the antiviral activity of interferons is dependent on normal activity of fatty acid cyclo-oxygenase. Thus, it is tempting to speculate that metabolic disturbances of long-chain essential fatty acid metabolism in atopic individuals might be linked to an impaired efficacy of thymus hormones in T cell maturation, a diminished PGE-mediated regulation of IgE synthesis and cutaneous T-cell infiltration, and a reduced antiviral activity of interferons.