Effect of cutaneous cell-mediated immune response to rIFN gamma on Mycobacterium leprae viability in the lesions of lepromatous leprosy.
1. Studies were carried out to determine the effect of intra-dermal injections of recombinant human interferon-gamma (rIFN gamma) on the viability of Mycobacterium leprae. Twenty-three untreated and 4 treated multibacillary patients, 12 with lepromatous leprosy (LL) and 15 with borderline lepromatous leprosy (BL), were selected for intradermal administration of rIFN gamma or PPD. Treated patients (LL and BL) had received multi-drug therapy according to the recommendations of the World Health Organization, i.e., rifampicin (600 mg/month), dapsone (100 mg/day) and clofazimine (50 mg/day and 300 mg/month) for 1-4 months. Three daily doses of 10 or 30 micrograms rIFN gamma induced local induration and mononuclear leucocyte accumulation. Bacteria isolated from a punch biopsy of the site 21 days after lymphokine administration were injected into mouse foot pads and evaluated for viability and growth. 2. The local response to rIFN gamma (specific activity 2 x 10(7) units/mg protein) induced a delay or total inhibition of M. leprae growth in the mouse foot pad, indicating that the cellular response to the antigen reduced local M. leprae viability. The extent of reduction in viability depended on the dose of rIFN gamma injected and the extent of local induration induced by the lymphokine. With a vigorous cell-mediated immune response growth was fully inhibited. 3. A similar but less extensive effect on M. leprae viability was observed in response to the local injection of 5 units in 0.1 ml of purified protein derivative of tuberculin (PPD).
Damasco
M H
MH
Unidade de Hanseníase, Fundacão Oswaldo Cruz, Rio de Janeiro, Brasil.
Sarno
E N
EN
Lobão
A S
AS
Alvarenga
F B
FB
Porto
J A
JA
Rosankaimer
F
F
Kaplan
G
G
D000818:Animals; D001681:Biological Assay; D004359:Drug Therapy, Combination; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000627:therapeutic use*; D015439:Leprosy, Borderline / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D015440:Leprosy, Lepromatous / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D011994:Recombinant Proteins; D012867:Skin / Q000187:drug effects* / Q000276:immunology*; D013997:Time Factors
D011994:Recombinant Proteins; D007371:Interferon-gamma