title: Thalidomide inhibits tumor necrosis factor-alpha production and antigen presentation by Langerhans cells.
abstract: Thalidomide is an effective treatment for several inflammatory and autoimmune disorders including erythema nodosum leprosum, Behcet's syndrome, discoid lupus erythematosus, and Crohn's disease. Thalidomide is believed to exert its anti-inflammatory effects, at least in part, by inhibiting tumor necrosis factor-alpha (TNF-alpha) production by monocytes. We studied the effects of thalidomide on epidermal Langerhans cells (LC). LCs are epidermal antigen-presenting dendritic cells that play important roles in skin immune responses. Using the murine epidermis-derived dendritic cell lines, XS106A from A/J mice and XS52 from BALB/c mice as surrogates for LC, we found that thalidomide inhibited TNF-alpha production in a concentration-dependent manner. Northern blot analysis revealed that thalidomide significantly decreased the peak-induced mRNA level of TNF-alpha in XS106A cells and XS52 cells. We then examined the effect of thalidomide on fresh LC enriched to approximately 98% using positive selection of Ia+ cells with antibodies conjugated to magnetic microspheres. TNF-alpha production was reduced by 67.7% at a thalidomide concentration of 200 microg per mL. Thalidomide also had a profound inhibitory effect on the ability of LC to present antigen to a responsive TH1 clone. Thalidomide inhibits TNF-alpha production and the antigen-presenting ability of epidermal LCs. These mechanisms may contribute to the therapeutic effects observed with this agent.
authors.affiliation: Department of Dermatology, Joan and Sanford I. Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Deng
authors.forename: Wanhong
authors.initials: W
authors.lastname: Ding
authors.forename: Richard D
authors.initials: RD
authors.lastname: Granstein
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D013792:Thalidomide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide