title: Effective treatment of erythema nodosum leprosum with thalidomide is associated with immune stimulation.
abstract: The immunomodulatory drug thalidomide is the treatment of choice for erythema nodosum leprosum (ENL), an inflammatory cutaneous and systemic complication of multibacillary leprosy. To elucidate the mechanism of action of thalidomide in this syndrome, we prospectively investigated 20 patients with ENL who were treated with thalidomide for 21 days. All patients responded to treatment, with the majority of them having complete resolution of cutaneous lesions within 7 days. This response was associated with a marked but transient increase in ex vivo mitogen-induced expression of interleukin (IL)-2 and interferon- gamma by CD4(+) and CD8(+) T cells that was observed on treatment day 7, but these returned to pretreatment levels by day 21. Plasma tumor necrosis factor- alpha levels were not high at baseline, and they increased modestly during treatment. Plasma levels of IL-12 increased steadily during thalidomide treatment. Hence, the therapeutic effect of thalidomide in ENL appears to be associated with transient immune stimulation, which suggests that the drug may promote an active immunoregulatory response.
authors.affiliation: Rockefeller University, New York, New York, USA. phaslett@med.miami.edu
authors.forename: Patrick A J
authors.initials: PA
authors.lastname: Haslett
authors.forename: Paul
authors.initials: P
authors.lastname: Roche
authors.forename: C Ruth
authors.initials: CR
authors.lastname: Butlin
authors.forename: Murdo
authors.initials: M
authors.lastname: Macdonald
authors.forename: Niraj
authors.initials: N
authors.lastname: Shrestha
authors.forename: Rakesh
authors.initials: R
authors.lastname: Manandhar
authors.forename: Joe
authors.initials: J
authors.lastname: Lemaster
authors.forename: Rachel
authors.initials: R
authors.lastname: Hawksworth
authors.forename: Mahesh
authors.initials: M
authors.lastname: Shah
authors.forename: A Steven
authors.initials: AS
authors.lastname: Lubinsky
authors.forename: Matthew
authors.initials: M
authors.lastname: Albert
authors.forename: Jason
authors.initials: J
authors.lastname: Worley
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000097:blood; D004893:Erythema Nodosum / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis; D007917:Leprostatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015440:Leprosy, Lepromatous / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000473:pathology; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D007917:Leprostatic Agents; D012333:RNA, Messenger; D013792:Thalidomide; D007371:Interferon-gamma