Central nervous system activation of the indoleamine-2,3-dioxygenase pathway in human T cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.
Human T cell lymphotropic virus type I (HTLV-I) is associated with a chronic neurologic disease called HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The potential mechanisms of HAM/TSP pathogenesis were assessed by examination of 2 pathways initiated by interferon-gamma, a predominant cytokine in HAM/TSP. Jamaican HAM/TSP patients (n=17) were compared with patients with other neurologic diseases (ONDs; n=13) with respect to cerebrospinal fluid levels of the following: neopterin; nitrite plus nitrate, a stable indicator of nitric oxide; and tryptophan and kynurenine, metabolites of the indoleamine-2,3-dioxygenase (IDO) pathway. HAM/TSP patients had significantly elevated levels of neopterin (P=.003) and kynurenine (P=.05) and a significantly decreased level of tryptophan (P=.003), compared with patients with ONDs. These results support immune activation within the central nervous system and activation of the IDO pathway. Thus, activation of the IDO pathway may play a role in HAM/TSP.
Maloney
E M
EM
Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20822, USA. maloneyb@epndce.nci.nih.gov
St Claire Morgan
O
O
Widner
B
B
Werner
E R
ER
Fuchs
D
D
D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000134:cerebrospinal fluid; D009569:Nitric Oxide / Q000502:physiology; D015493:Paraparesis, Tropical Spastic / Q000209:etiology* / Q000378:metabolism; D014364:Tryptophan / Q000134:cerebrospinal fluid; D014366:Tryptophan Oxygenase / Q000502:physiology*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009569:Nitric Oxide; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan; D014366:Tryptophan Oxygenase