Intraventricular infusion of antagonists of IL-1 and TNF alpha attenuates neurodegeneration induced by the infection of Trypanosoma brucei.
Infection of Trypanosoma brucei causes specific patterns of neurodegeneration in association with chronic expression of proinflammatory cytokines in the brain. To investigate whether the induction of proinflammatory cytokines contributed to the observe pathology in this disease, we infected rats with T. brucei and treated them with intracerebral infusion of the cytokine antagonists interleukin-1 receptor antagonist (IL-1ra) and/or soluble type-I receptor of the tumor necrosis factor (sTNFr1). Infusion of IL-1ra, not sTNFr1, restored the reduction of body weight gain induced by the infection. Infusion of IL-1ra+sTNFr1 reduced the expression of IL-1beta and the cytokine response gene IkappaBalpha, but not TNFalpha. Infusion of sTNFr1 reduced trypanosome-induced neurodegeneration. Further reduction of neurodegeneration was seen after IL-1ra+sTNFr1 infusion. Infusion of IL-1ra alone, however, did not significantly affect the patterns of neurodegeneration. These results suggest that TNFalpha is a major mediator for trypanosome-induced neurodegeneration although its neurotoxic effects can be augmented by IL-1.
Section of Oral Biology, Ohio State University Health Science Center, Columbus, OH, USA. quan.14@osu.edu
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D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage; D001835:Body Weight / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D007276:Injections, Intraventricular; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D019636:Neurodegenerative Diseases / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D047888:Receptors, Tumor Necrosis Factor, Type I; D012795:Sialoglycoproteins / Q000008:administration & dosage; D012995:Solubility; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha