ABSTRACT
AIM: To introduce Granulocyte-colony stimulating factor (G-CSF) as a new therapeutic modality for schistosomiasis through stem cell mobilization, immunomodulation or fibrosis remodeling. METHODS: In this study, a 5 d course of human recombinant G-CSF (100 µg/kg sc) was applied to Schistosoma mansoni-infected mice at different stages of disease (5 d before infection as well as 3, 5 and 7 wk post-infection). The animals were sacrificed at 10 d as well as 4, 6 and 8 wk post infection. Mice were examined for: (1) Total leukocyte count which is an accepted surrogate marker for the stem cell mobilization into the circulation; (2) Egg count in intestine and liver tissue to assess the parasitic load; and (3) Histopathological changes in Hx/E and Masson trichrome stained sections as well as collagen content in Sirius red-stained liver sections to determine the severity of liver fibrosis. RESULTS: Mice developed leukocytosis. The egg load and the number of granulomas were not affected by the G-CSF treatment but there was an obvious change in the composition of granulomas towards an increased cellularity. Moreover, fibrosis was significantly decreased in treated groups compared to untreated animals (collagen content either preinfection or at 3 and 5 wk post infection: 5.8 ± 0.5, 4.7 ± 0.5, 4.0 ± 0.7 vs 8.2 ± 0.9; P ≤ 0.01). CONCLUSION: Although G-CSF did not cause direct elimination of the parasite, it enhanced granulomatous reaction and reduced the fibrosis. Further investigation of the underlying mechanisms of these two actions is warranted.
ABSTRACT
Dry cough, dyspnea and manifestations of bronchial asthma have recently been observed in patients with acute schistosomiasis. To investigate the type and pathogenesis of these conditions, an experimental mouse model for acute schistosomiasis was used. Forty mice were divided into four groups of ten each: three infected groups and a non-infected control group. The animals were examined 7, 28-35 and 40 days after exposure to cercariae. During the acute phase of the infection (28-35 days), a process of multifocal interstitial pneumonitis involving the peribronchial, peribronchiolar and subpleural tissues was found. This process was not seen during the other phases of the infection. Indirect immunofluorescence failed to demonstrate the presence of schistosomal antigens in the acute-phase lesions. The pneumonitis was attributed to products (inflammatory mediators) from acute-phase periovular necrotic-inflammatory lesions in the liver that were transported to the lungs by the bloodstream.
Recentemente tem sido observada a presença de tosse seca, dispnéia, e manifestações de asma brônquica em pacientes com esquistossomose aguda. Para se investigar sobre o tipo e patogenia de tais lesões foi utilizado um modelo experimental de esquistossomose aguda no camundongo. Quarenta animais foram divididos em quatro grupos de 10 animais cada, 3 infectados e um grupo controle não-infectados. Os exames foram feitos após 7, 28-35, e 40 dias após a exposição cercariana. Na fase aguda da infecção (28-35 dias), encontrou-se um processo de pneumonite intersticial multifocal, envolvendo os tecidos peribrônquicos, peribronquiolares e subpleural, processo que esteve ausente nas outras fases examinadas. Não foi possível a demonstração de antígenos do Schistosoma. mansoni nas lesões da fase aguda, através da técnica de imuno-fluorescência indireta. A pneumonite foi atribuída a produtos (mediadores inflamatórios) gerados nas lesões hepáticas necro-inflamatórias periovulares da fase aguda, e transportados para os pulmões pela circulação sanguínea.
