Mycobacterium leprae DNA content, cellular and cytokine patterns in skin lesions of leprosy patients undergoing multidrug therapy (MDT).
Skin biopsies from untreated and MDT-treated patients were examined for infiltrating cells and cells producing the cytokines TNF-alpha, IFN-gamma, and IL-1 beta using immunohistochemistry. Biopsy specimens from untreated tuberculoid leprosy patients were characterized by the presence of cells producing TNF-alpha, IFN-gamma, and IL-1 beta and of subepidermal Langerhans cells. These cells were rarely found or completely absent in biopsies of untreated lepromatous leprosy patients, but tended to increase under MDT. In a short-term therapy trial for three months with brodimoprim, dapsone, and rifampicin, 12 patients were monitored by follow-up biopsies. Semiquantitative PCR for mycobacterial DNA revealed two groups of patients: one group in which mycobacterial DNA in follow-up biopsies remained constant and a second group in which a decrease of mycobacterial DNA during therapy was noted. Immunophenotyping in these follow-up biopsies revealed that in the latter group IFN-gamma-positive cells and Langerhans cells were present and gamma delta T cell receptor-positive cells tended to decrease during therapy. In contrast, in patients whose mycobacterial DNA did not change during therapy, these phenotypical manifestations were not observed. We therefore, conclude that assessment of mycobacterial DNA in combination with phenotyping of infiltrating cells and determination of cytokine patterns may be useful tools in establishing criteria for the effectiveness and duration of MDT in patients with leprosy.
Flad
H D
HD
Department of Immunology and Cell Biology, Forschungsinstitut Borstel, Germany.
Richter
E
E
Schlüter
C
C
Duchrow
M
M
Arnoldi
J
J
Hahn
M
M
Graf von Ballestrem
W
W
Alvarenga
A E
AE
Gerdes
J
J
D000900:Anti-Bacterial Agents; D016207:Cytokines / Q000378:metabolism*; D004269:DNA, Bacterial / Q000032:analysis* / Q000235:genetics; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007801:Langerhans Cells / Q000473:pathology; D007918:Leprosy / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology*; D009166:Mycobacterium leprae / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000382:microbiology / Q000473:pathology
D000900:Anti-Bacterial Agents; D016207:Cytokines; D004269:DNA, Bacterial; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma