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 | Patrick A J Haslett, Paul Roche, C Ruth Butlin, Murdo Macdonald, Niraj Shrestha, Rakesh Manandhar, Joe Lemaster, Rachel Hawksworth, Mahesh Shah, A Steven Lubinsky, Matthew Albert, Jason Worley, Gilla Kaplan |
Journal | The Journal of infectious diseases
(J Infect Dis)
Vol. 192
Issue 12
Pg. 2045-53
(Dec 15 2005)
ISSN: 0022-1899 [Print] United States |
PMID | 16288366
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Cytokines
- Immunologic Factors
- Leprostatic Agents
- RNA, Messenger
- Thalidomide
- Interferon-gamma
|
Topics |
- Adolescent
- Adult
- CD4-Positive T-Lymphocytes
(immunology)
- CD8-Positive T-Lymphocytes
(immunology)
- Cytokines
(blood)
- Erythema Nodosum
(drug therapy, immunology, pathology)
- Flow Cytometry
- Gene Expression
- Humans
- Immunologic Factors
(pharmacology, therapeutic use)
- Interferon-gamma
(biosynthesis)
- Leprostatic Agents
(pharmacology, therapeutic use)
- Leprosy, Lepromatous
(drug therapy, immunology, pathology)
- Male
- Middle Aged
- Prospective Studies
- RNA, Messenger
(analysis)
- Reverse Transcriptase Polymerase Chain Reaction
- Skin
(pathology)
- Thalidomide
(pharmacology, therapeutic use)
|