02610nas a2200385   4500000000100000008004100001260000900042653001000051653002300061653002000084653001800104653001100122653002900133653003800162653001900200653002200219653001800241653001800259653002800277653002400305653000900329653003700338653002800375653001600403653003200419100001400451700001300465700001600478700001300494245014000507300001100647490000700658520154500665022001402210       2008                            d  c200810aAdult10aC-Reactive Protein10aCells, Cultured10aDexamethasone10aHumans10aImmunosuppressive Agents10aIntercellular Adhesion Molecule-110aInterleukin-1010aInterleukin-1beta10aInterleukin-610aInterleukin-810aLeukocytes, Mononuclear10aLipopolysaccharides10aMale10aReceptors, Tumor Necrosis Factor10aSerum Amyloid A Protein10aThalidomide10aTumor Necrosis Factor-alpha1 aShannon E1 aNoveck R1 aSandoval FG1 aKamath B00aThalidomide suppressed IL-1beta while enhancing TNF-alpha and IL-10, when cells in whole blood were stimulated with lipopolysaccharide.  a447-570 v303 a<p>Thalidomide is used to treat erythema nodosum leprosum (ENL). The events that precipitate this inflammatory reaction, which may occur in multibacillary leprosy patients, and the mechanism by which thalidomide arrest ENL, are not known. Thalidomide's ability to inhibit tumor necrosis factor alpha (TNF-alpha) in vitro has been proposed as a partial explanation of its effective treatment of ENL. In in vitro assays, thalidomide can enhance or suppress TNF-alpha. This is dependent on the stimulant used to evoke TNF-alpha; the procedure used to isolate the mononuclear cells from blood, and the predominant mononuclear cell type in the culture. To avoid artifacts that may occur during isolation of mononuclear cells from blood, we stimulated normal human blood with LPS and evaluated the effect of thalidomide and dexamethasone on TNF-alpha, and other inflammatory cytokines and biomarkers. Thalidomide suppressed interleukin 1 beta (IL-1beta) (p = 0.007), and it enhanced TNF-alpha (p = 0.007) and interleukin 10 (IL-10) (p = 0.031). Dexamethasone enhanced IL-10 (p = 0.013) and suppressed IL-1beta, TNF-alpha, interleukin 6 (IL-6), and interleukin 8 (IL-8) (p = 0.013). The two drugs did not suppress: C-reactive protein (CRP), Ig-superfamily cell-adhesion molecule 1 (ICAM 1), tumor necrosis factor receptor 1 (TNFR1), tumor necrosis factor receptor 2 (TNFR2), or amyloid A. In vitro and in vivo evidence is accumulating that TNF-alpha is not the primary cytokine targeted by thalidomide in ENL and other inflammatory conditions.</p>  a1532-2513