The systemic influence of recombinant interleukin 2 on the manifestations of lepromatous leprosy.
14 patients with lepromatous leprosy received twice daily injections of 10 micrograms recombinant interleukin 2 (rIL-2), by the intradermal route, in the skin of the back for 8 d (total dose, 160 micrograms). Lymphokine administration was accomplished without drug toxicity, or the development of acute nerve damage. The majority of patients developed nontender axillary lymphadenopathy during the course of treatment. Local injection sites showed progressively larger zones of induration, peaking at 24 h and persisting for many days. Early 12-h reactions were of a macular, erythematous nature and exhibited an increasingly striking diurnal variation. The morning injection sites were three- to fourfold larger in diameter than those placed in the evening (9 am to 9 pm). Systemic manifestations of intradermal rIL-2 administration were noted. Peripheral blood T cells, including CD4+ and CD8+ phenotypes, increased 2-2.5-fold and NK cells increased sixfold. Elevations in [3H]TdR incorporation into peripheral blood mononuclear cells occurred to a variety of mycobacterial antigens, but not to those of Mycobacterium leprae. Within 2 wk, biopsies at sites far removed from the back showed increased infiltration of mononuclear cells in 12 of 14 patients. Immunocytochemistry revealed the presence of newly emigrated CD4+ T cells, monocytes, and dermal CD1+ Langerhans cells. Endothelial cells of small dermal vessels expressed major histocompatibility complex class II determinants on their surface. Transmission electron microscopy of these specimens revealed markedly enlarged endothelial cells with many surface projections extending into the lumen as well as extravasating lymphoid cells. The numbers of acid-fast M. leprae in the peripheral sites were examined by slit smear and in biopsies of matched leprosy lesions taken before and after IL-2 administration. Within 2 mo, slit smears showed a 0.5 log or greater reduction in 12 of 14 patients, with a mean for all patients tested of 0.5 log units. Biopsy specimens showed a 1 log unit or greater reduction in the bacterial index (B.I.) in 6 of 14 patients. Historical controls in this Nepalese population showed a 0.5 log unit reduction after multidrug therapy over a period of 12 mo. Thus, after 8 d of IL-2 injections, a fivefold reduction in B.I. was observed during the first 2 mo of the study. Antibody levels against M. leprae phenolic glycolipid 1 (PGL-1) and lipoarabinomanan B were markedly elevated after IL-2 injections, while PGL-1 antigen levels were reduced. We conclude that the administration of rIL-2 has had a significant effect in decreasing the total body burden of M. leprae.(ABSTRACT TRUNCATED AT 400 WORDS)
Kaplan
G
G
Rockefeller University, New York, New York 10021.
Britton
W J
WJ
Hancock
G E
GE
Theuvenet
W J
WJ
Smith
K A
KA
Job
C K
CK
Roche
P W
PW
Molloy
A
A
Burkhardt
R
R
Barker
J
J
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000032:analysis; D000942:Antigens, Bacterial / Q000032:analysis; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000008:administration & dosage*; D015440:Leprosy, Lepromatous / Q000628:therapy*; D007958:Leukocyte Count; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007376:Interleukin-2; D011994:Recombinant Proteins