TNF-alpha is expressed at sites of parasite and tissue destruction in the spleen of mice acutely infected with Trypanosoma cruzi.
Mice infected with a macrophagotropic strain of Trypanosoma cruzi develop progressive splenomegaly due to reactive hyperplasia with increased number of lymphocytes and macrophages, culminating in parasite disintegration and necrosis of parasitized cells. Necrotic changes have been attributed to the liberation of toxic cytokines, including TNF-alpha, from parasitized macrophages. In the present study, the presence of TNF-alpha was investigated in situ. In addition the participation of destroyed parasites in inducing the liberation of TNF-alpha was examined in two highly susceptible mice strains (C3H and Swiss) and a more resistant strain (DBA). Swiss (90) C3H/He (83) and DBA (30) mice were infected with the Peruvian strain of T. cruzi. Nineteen infected Swiss mice, and 22 infected C3H/He were treated with Benznidazole (one or two doses, 100 mg/kg bw/day), on the 8th and 9th days after infection. Necrotic splenic lesions occurred in both susceptible and resistant strains of mice. Although differing in degree, lesions were more intense in C3H and Swiss than in DBA mice. Comparing untreated and treated susceptible mice, necrotic lesions were significantly less intense in the latter. By specific monoclonal antibody immunolabelling, TNF-alpha was demonstrated in the cytoplasm of macrophages and within necrotic areas, from Swiss, C3H/He and DBA mouse spleens. In conclusion, TNF-alpha, probably synthesized by macrophages, was strongly expressed at the sites of parasite and cell destruction, thus appearing to play a pivotal role in splenic necrotic changes associated with severe experimental T. cruzi infection.
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Centro de Pesquisas Gonçalo Moniz/Fiocruz, Salvador, Bahia, Brazil.
Andrade
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Andrade
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D000208:Acute Disease; D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004198:Disease Susceptibility; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009336:Necrosis; D009593:Nitroimidazoles / Q000627:therapeutic use; D018512:Parasitemia / Q000378:metabolism; D013154:Spleen / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D014344:Trypanocidal Agents / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D014409:Tumor Necrosis Factor-alpha; C009999:benzonidazole