Central Nervous System Activation of the Indoleamine‐2,3‐Dioxygenase Pathway in Human T Cell Lymphotropic Virus Type I–Associated Myelopathy/Tropical Spastic Paraparesis

Abstract

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.

Expression of indoleamine 2,3‐dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons

“…The first and regulatory enzyme of the KP, indoleamine 2,3‐dioxygenase (IDO) (EC 1.13.11.17), has been shown to be increased in several brain diseases such as AIDS dementia complex (Sardar and Reynolds, 1995; Smith et al, 2001; Burudi et al, 2002), viral brain infection (Heyes et al, 1992; Maloney et al, 2000), brain abscesses (Schroten et al, 2001), cerebral malaria (Hansen et al, 2000), Alzheimer's disease (Guillemin et al, 2003a), epilepsy (Nakano et al, 1992), and glioblastoma (Uyttenhove et al, 2003). IDO can be strongly induced by inflammatory cytokines such as interferon‐γ (IFN‐γ), and to a lesser extent by TNF‐α and IFN‐α (Heyes et al, 1997a; Pemberton et al, 1997).…”

Cerebrospinal fluid neopterin in paediatric neurology: a marker of active central nervous system inflammation

“…In adult neurology, CSF neopterin is a useful marker of CNS infection and inflammation, 6 particularly in assessing human immunodeficiency virus encephalopathy and its treatment 7,8 . CSF neopterin is also elevated in acute infection (bacterial meningitis and viral encephalitis), 6 chronic infection (subacute sclerosing panencephalitis, human T‐cell lymphotropic virus type 1), 9,10 and chronic inflammatory disorders (sarcoidosis and neuro‐Behçets) 2,11 . CSF neopterin also has some uses in demyelinating disorders such as multiple sclerosis, although its sensitivity is very dependent on the activity of demyelination at the time of testing 12,13 …”