INTERFERON (IFN)-ALPHA, IFN-GAMMA, INTERLEUKIN (IL)-2, AND ARACHIDONIC-ACID METABOLITES MODULATE IL-4-INDUCED IGE SYNTHESIS SIMILARLY IN HEALTHY-PERSONS AND IN ATOPIC-DERMATITIS PATIENTS

The role of cytokines and arachidonic acid metabolites in the regulati on of IgE production in healthy persons and in atopic dermatitis patie nts with elevated IgE levels was studied. Interleukin-4 (IL-4) induced IgE production in peripheral blood mononuclear cells (PBMCs) of all d onors, and no significant difference was found between the amounts of IgE produced by healthy persons and atopic dermatitis patients. Simila rly, recombinant interferon (IFN)-alpha and IFN-gamma, as well as IL-2 , inhibited IL-4-induced IgE production to a similar extent in both st udy groups. To evaluate the role of arachidonic acid (AA) metabolites in the regulation of IgE production, we added indomethacin, an inhibit or of the cyclooxygenase pathway, or nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway, to IL-4-treated cultures. B oth indomethacin and NDGA strongly inhibited IL-4-induced IgE producti on. They also inhibited IL-4-induced IgG4 synthesis. No significant di fference in the amount of inhibition was found between the two study g roups. We were unable to restore the NDGA-induced inhibition of IgE-pr oduction by adding leukotrienes B4, C4, D4, or 5-HETE to the NDGA-trea ted cultures. PGE, also failed to restore the indomethacin-mediated in hibitory effect. Consequently, NDGA- and indomethacin-mediated inhibit ory effects do not appear to be mediated by any single factor studied. Collectively, our results show IFNs and IL-2 to be similar in effect in the modulation of IL-4-induced IgE synthesis in healthy and atopic persons. In addition, our results show the importance of AA metabolite s in the regulation of IgE and IgG4 synthesis in normal persons as wel l as in atopic dermatitis patients.