Pentoxifylline down-regulates adhesion molecule expression and inflammatory cytokine production in cultured peripheral blood mononuclear cells from patients with HTLV-I-associated myelopathy.
To clarify if pentoxifylline (PTX) may have therapeutic potential for human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM), we investigated the in vitro effect of PTX on spontaneous proliferation of peripheral blood lymphocytes (SPP), as well as on the expression of adhesion molecules, such as lymphocyte function antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4), and the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and granulocyte-monocyte colony stimulating factor (GM-CSF), in cultured PBMC from 10 HAM patients, compared with control subjects. SPP in HAM patients was significantly suppressed in a dose-dependent manner with PTX. Using flow cytometry, PTX was found to down-regulate the expression of LFA-1 and VLA-4 on CD4+ and CD8+ T cells in HAM patients as well as control subjects. However, the fall in the expression of LFA-1 and VLA-4 on CD4+ T cell population in HAM patients was higher than that of control subjects. PTX caused a significant suppression of spontaneous production of TNF-alpha by cultured PBMC of HAM patients. It also caused a small but significant suppression GM-CSF and IFN-gamma production. Collectively, our results suggest that PTX might be therapeutically effective at critical points in the immunopathogenesis of HAM.
Tsujino
A
A
First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
Nakamura
T
T
Nishiura
Y
Y
Shirabe
S
S
Furuya
T
T
Goto
H
H
Kawakami
A
A
Eguchi
K
K
Nagataki
S
S
D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015493:Paraparesis, Tropical Spastic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D012016:Reference Values
D015704:CD4 Antigens; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D010726:Phosphodiesterase Inhibitors; D010431:Pentoxifylline