Pentoxifylline decreases in vivo and in vitro tumour necrosis factor-alpha (TNF-alpha) production in lepromatous leprosy patients with erythema nodosum leprosum (ENL).
Increasing evidence has implicated TNF-alpha as a pivotal molecule involved in the systemic inflammatory manifestations of ENL, an acute inflammatory complication that may occur in the chronic course of leprosy. In the present study, the mechanism of action of pentoxifylline (PTX) as an alternative therapy for management of leprosy reactions has been evaluated. The effect of PTX on TNF-alpha production was examined in leprosy patients at the protein level and at the transcriptional level as well. Treatment of ENL patients with PTX (1200 mg daily) ameliorated the systemic symptoms and favoured the evolution of reactional leprosy lesions. Serum TNF-alpha was assayed before and during treatment with PTX in 15 patients. The increased TNF-alpha levels seen in the circulation during the reaction were dramatically reduced within 3-7 days of therapy. No significant effect on serum IL-6 was noted. In vitro TNF-alpha production was assayed upon culture stimulation with Mycobacterium leprae. A reduction of inducible TNF-alpha in peripheral blood mononuclear cells (PBMC) was seen after 1-2 weeks of in vivo administration of PTX. Furthermore, no effect of the drug on IL-10 secretion was detected in these cultures. A kinetic analysis of the expression of TNF-alpha and IL-6 mRNA at the site of leprosy lesion was performed in six reactional patients by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The amount of TNF-alpha mRNA was increased in the tissue during ENL compared with before the reaction, and decreased thereafter following treatment for reaction (either PTX or thalidomide). These data suggest that PTX inhibits TNF-alpha production in ENL patients both in vivo and in vitro, and it may be useful in the treatment of leprosy patients undergoing ENL.
Sampaio
E P
EP
Leprosy Laboratory, Oswaldo Cruz Institute, Rio de Janeiro, Brazil.
Moraes
M O
MO
Nery
J A
JA
Santos
A R
AR
Matos
H C
HC
Sarno
E N
EN
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D004893:Erythema Nodosum / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015440:Leprosy, Lepromatous / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline