A new approach for the pathogenesis of human African trypanosomiasis.

From Trypanosoma brucei brucei, a molecule has been isolated which triggers the production of IFN-gamma by CD8+ T-cells. IFN-gamma modulates events in the hosts immune- and nervous system and provides a growth stimulus for the parasites. Furthermore, a molecule with IFN-gamma-like immunoreactivity has been detected in rat dorsal root ganglion cells and certain neurons in the brain. This neuron-derived IFN-gamma-like molecule differs in molecular weight from lymphocyte-derived IFN-gamma but shares important biological activities with the latter, which includes a growth stimulus for trypanosomes. Trypanosomes localized to sensory ganglia and infected rats develop a severe thermal hyperalgesia. Intrathecal injection of IFN-gamma causes in rats a sustained phase of nociceptive flexor reflex facilitation, which can be partially blocked by nitro-L-arginin-ester, an inhibitor of nitric oxide synthase, indicating that nociceptive effects of the IFN-gamma is mediated by activation of the L-arginin-nitric oxide pathway.