Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients.
10 patients with borderline and lepromatous leprosy were selected for a prolonged trial with recombinant interferon gamma (rIFN-gamma). Patients received 30 micrograms intradermally for six injections over a 9-d period, and then either 100 micrograms intradermally every 1 mo for 10 mo or every 2 wk for 5 mo (total, 1.2 mg). Erythema nodosum leprosum (ENL) was induced in 60% of the patients within 6-7 mo, as compared with an incidence of 15% per year with multiple drug therapy alone. The mean whole-body reduction in bacterial index over the first 6 mo was 0.9 log units. Cutaneous induration at the intradermal injection sites of greater than or equal to 15 mm predicted the development of a subsequent reactional state. Monocytes obtained from patients receiving the lymphokine demonstrated an increased respiratory burst and a 2.5-5.1-fold increase in tumor necrosis factor alpha (TNF-alpha) secretion in response to agonists. Patients in ENL had an even higher release of TNF-alpha from monocytes as well as high levels of TNF-alpha in the plasma (mean, 2,000 pg/ml). Thalidomide therapy was required to treat the systemic manifestations of ENL. Control of toxic symptoms with thalidomide was associated with a 50-80% reduction in agonist-stimulated monocyte TNF-alpha secretion. IFN-gamma enhanced the monocyte release of TNF-alpha by 3-7.5-fold (agonist dependent) when added to patient's cells in vitro, and this could be suppressed by the in vitro addition of 10 micrograms/ml of thalidomide.
Sampaio
E P
EP
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
Moreira
A L
AL
Sarno
E N
EN
Malta
A M
AM
Kaplan
G
G
D004893:Erythema Nodosum / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000009:adverse effects* / Q000627:therapeutic use; D015439:Leprosy, Borderline / Q000473:pathology / Q000628:therapy*; D015440:Leprosy, Lepromatous / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins; D012867:Skin / Q000473:pathology; D013792:Thalidomide / Q000627:therapeutic use*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D007371:Interferon-gamma