Effect of thalidomide on the expression of TNF-alpha m-RNA and synthesis of TNF-alpha in cells from leprosy patients with reversal reaction.
Hypersensitivity reactions called reversal reaction (RR) and erythema nodosum leprosum (ENL) occur in leprosy. They are characterized by an increase in tumor necrosis factor-alpha (TNF-alpha). Thalidomide is an effective treatment for ENL but not RR. Its effectiveness in ENL is attributed to inhibition of TNF-alpha, and this does not explain its failure to treat RR. We assessed thalidomide's effect on TNF-alpha in RR. Mononuclear cells from RR and non-RR patients and healthy individuals were treated with thalidomide and M.leprae (AFB), a cytosol fraction of M. leprae or Dharmendra lepromin. Thalidomide suppressed TNF-alpha, but when some RR patients' cells were stimulated with AFB, it enhanced TNF-alpha.
Tadesse
Azeb
A
Armauer Hansen Research Institute, Addis Ababa, Ethiopia. Azeb.tadesse@mssm.edu
Abebe
Markos
M
Bizuneh
Elizabeth
E
Mulugeta
Wondwossen
W
Aseffa
Abraham
A
Shannon
E J
EJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004893:Erythema Nodosum / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D005260:Female; D006801:Humans; D007916:Lepromin / Q000276:immunology / Q000494:pharmacology; D007918:Leprosy / Q000097:blood / Q000150:complications / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013792:Thalidomide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000942:Antigens, Bacterial; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007916:Lepromin; D013792:Thalidomide