Central nervous system activation of the indoleamine-2,3-dioxygenase pathway in human T cell lymphotropic virus type I-associated myelopathy/tropicalspastic paraparesis

Human T cell lymphotropic virus type I (HTLV-I) is associated with a chroni c neurologic disease called HTLV-I-associated myelopathy/tropical spastic p araparesis (HAM/TSP). The potential mechanisms of HAM/TSP pathogenesis were assessed by examination of 2 pathways initiated by interferon-gamma, a pre dominant cytokine in HAM/TSP. Jamaican HAM/TSP patients (n = 17) were compa red with patients with other neurologic diseases (ONDs; n = 13) with respec t to cerebrospinal fluid levels of the following: neopterin; nitrite plus n itrate, a stable indicator of nitric oxide; and tryptophan and kynurenine, metabolites of the indoleamine-2,3-dioxygenase (IDO) pathway. HAM/TSP patie nts had significantly elevated levels of neopterin (P = .003) and kynurenin e (P = .05) and a significantly decreased level of tryptophan (P = .003), c ompared with patients with ONDs, These results support immune activation wi thin the central nervous system and activation of the IDO pathway. Thus, ac tivation of the IDO pathway may play a role in HAM/TSP.