ABSTRACT
Dehydroepiandrosterone (DHEA) is a native neurosteroid with immunomodulating activity. DHEA effectively protects animals from several viral, bacterial and parasitic infections and it was suggested that its age-associated decline is related with immunosenescence. In the present study we examined the ability of DHEA to inhibit the production of inflammatory mediators by mycoplasma-stimulated glial cells and to change the course of acute central nervous system (CNS) inflammatory disease in vivo. Addition of DHEA (10 microg/ml) markedly inhibited tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) production (98 and 95%, respectively), whereas nitric oxide (NO) and prostaglandin E2 (PGE2) production was not affected. However, daily administration of 0.5 mg DHEA to mice or 5 mg to rats did not change the clinical outcome of experimental autoimmune encephalomyelitis (EAE).
Subject(s)
Adjuvants, Immunologic/pharmacology , Astrocytes/metabolism , Dehydroepiandrosterone/pharmacology , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Interleukin-6/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesis , Animals , Anti-Inflammatory Agents/pharmacology , Astrocytes/cytology , Astrocytes/immunology , Cells, Cultured , Corticosterone/pharmacology , Dexamethasone/pharmacology , Dinoprostone/biosynthesis , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Glucocorticoids/pharmacology , Immunization , Mice , Mice, Inbred BALB C , Neuroimmunomodulation/drug effects , Neuroimmunomodulation/immunology , Nitric Oxide/biosynthesis , Rats , Rats, Inbred LewABSTRACT
Thalidomide selectively inhibits the production of human monocyte tumor necrosis factor alpha (TNF-alpha) when these cells are triggered with lipopolysaccharide and other agonists in culture. 40% inhibition occurs at the clinically achievable dose of the drug of 1 micrograms/ml. In contrast, the amount of total protein and individual proteins labeled with [35S]methionine and expressed on SDS-PAGE are not influenced. The amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony-stimulating factor produced by monocytes remain unaltered. The selectivity of this drug may be useful in determining the role of TNF-alpha in vivo and modulating its toxic effects in a clinical setting.