01888nas a2200277   4500000000100000008004100001260001300042653002000055653002500075653001100100653002800111653002400139653002500163653003700188653001600225653003200241100001500273700001300288700001400301700002100315245012300336300001100459490000700470520111900477022001401596       1999                            d  c1999 Nov10aCells, Cultured10aDepression, Chemical10aHumans10aLeukocytes, Mononuclear10aLipopolysaccharides10aMycobacterium leprae10aReceptors, Tumor Necrosis Factor10aThalidomide10aTumor Necrosis Factor-alpha1 aSantos D O1 aLorré K1 aDe Boer M1 aVan Heuverswyn H00aShedding of soluble receptor for tumor necrosis factor alpha induced by M. leprae or LPS from human mononuclear cells.  a185-930 v683 a<p>Cell surface expression and release of the tumor necrosis factor receptor (TNFR type I) was analyzed after stimulation of peripheral blood mononuclear cells (PBMC) with Mycobacterium leprae (M. leprae) or lipopolysaccharide (LPS). A transient spontaneous expression of TNFR type I on the surface of PBMC was observed. Two hr after activation with LPS, a significant reduction of TNFR type I expression was detected: Release of TNFR type I by M. leprae or LPS-stimulated PBMC was evaluated with an enzyme-linked immunoabsorbent assay. This release occurred relatively later (20 to 40 hr) than the secretion of TNF alpha which reached high levels between 8 to 20 hr after activation. Thalidomide, a potent drug for the treatment of erythema nodosum leprosum episodes by inhibiting TNF alpha production, had no influence on the TNFR type I expression. Similar results were obtained with pentoxifylline. It is concluded that the release of TNFR type I by M. leprae or LPS-stimulated PBMC may counteract the pro-inflammatory activities of TNF alpha, by reducing the systemic toxicity of this cytokine in leprosy.</p>  a1342-3681