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

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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-γ, 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.

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