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.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017950:Ganglia, Sensory / Q000469:parasitology; D005727:Ganglia, Spinal / Q000378:metabolism / Q000469:parasitology; D006133:Growth Substances / Q000096:biosynthesis; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology; D007278:Injections, Spinal; D007371:Interferon-gamma / Q000008:administration & dosage / Q000096:biosynthesis / Q000494:pharmacology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester; D009474:Neurons / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D014346:Trypanosoma brucei brucei / Q000378:metabolism / Q000502:physiology; D014353:Trypanosomiasis, African / Q000209:etiology*
D004791:Enzyme Inhibitors; D006133:Growth Substances; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester