Remodeling of hepatic vascular changes after specific chemotherapy of schistosomal periportal fibrosis

Andrade, Zilton A.; Baptista, Ana Paula; Santana, Thaynã Souto

doi:10.1590/s0074-02762006000900041

Cited by 24 publications

(29 citation statements)

References 19 publications

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“…In addition, the lack of a characteristic pattern of fibrosis reversal emphasizes the need for further in-depth analyses of the factors involved. The lack of complete reversion following chemotherapy has already been described in reports of human studies (12,23,33) and mouse studies (3,4). Comparison of old and young patients with respect to the time factor related to fibrosis regression among the treated cases was not considered, because in our study only 4.4% of subjects were less than 20 years of age.…”

Section: Vol 52 2008 Cytokine Production and Morbidity In Schistosomentioning

confidence: 76%

Effect of Chemotherapy with Praziquantel on the Production of Cytokines and Morbidity Associated with Schistosomiasis Mansoni

Martins-Leite

Gazzinelli

Alves-Oliveira

et al. 2008

Antimicrob Agents Chemother

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The objective of the present study was to test the hypothesis that treatment of schistosomiasis mansoni with praziquantel can alter significantly the immune response of patients and generate a reversal of the level of fibrosis. Peripheral blood mononuclear cell (PBMC) samples were collected from, and abdominal ultrasound examinations conducted on, volunteers infected with Schistosoma mansoni and living in an area where the disease is endemic, both prior to and one year after treatment with praziquantel. Subjects were classified into groups according to the level of pathology (i.e., absent, incipient, moderate, or severe fibrosis). PBMCs were stimulated with schistosome soluble egg antigens (SEA), and the levels of production of the cytokines gamma interferon (IFN-␥), tumor necrosis factor alpha, transforming growth factor ␤, and interleukin-4 (IL-4), IL-10, and IL-13 were determined. The chemotherapy was effective in reducing morbidity, particularly for individuals presenting with severe fibrosis. When levels of cytokine production in posttreatment PBMC cultures stimulated by SEA were categorized as low or high, significant differences in the distribution of IL-13 levels between groups presenting with or not presenting with fibrosis were established. Comparison of pre-and posttreatment SEA-induced cytokine levels in individuals who had experienced no change in the grade of fibrosis following chemotherapy revealed that the level of IFN-␥ decreased in subjects with fibrosis whereas that of IL-10 decreased in individuals with and without fibrosis. The data suggest that chemotherapy is effective in reducing the morbidity of the disease and that the level of IL-13 may be a useful indicator of the persistence of fibrosis following treatment.

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Section: Vol 52 2008 Cytokine Production and Morbidity In Schistosomentioning

confidence: 76%

Effect of Chemotherapy with Praziquantel on the Production of Cytokines and Morbidity Associated with Schistosomiasis Mansoni

Martins-Leite

Gazzinelli

Alves-Oliveira

et al. 2008

Antimicrob Agents Chemother

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“…The effect of treatment on cytokine profile and its relationship to anemia and nutritional morbidity reversal would be an important question to address given that hepatic vascular remodeling has been shown to occur after treatment in studies in animal models of schistosomiasis. 20,30,31 Exploring other cytokines not included in this study (i.e., IL-4, IL-5, and IL-13) and important in understanding the immune response to multiple parasitic infections should be integrated in future research efforts. 20 In summary, we have shown age-specific variation in serum cytokine profiles among children with S. haematobium and other chronic parasitic infections.…”

Section: Discussionmentioning

confidence: 99%

Age-Stratified Profiles of Serum IL-6, IL-10, and TNF-α Cytokines Among Kenyan Children with Schistosoma haematobium, Plasmodium falciparum, and Other Chronic Parasitic Co-Infections

Bustinduy¹,

Sutherland²,

Chang-Cojulun³

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. In a study of children having polyparasitic infections in a Schistosoma haematobium-endemic area, we examined the hypothesis that S. haematobium-positive children, compared with S. haematobium-negative children (antisoluble worm antigen preparation [SWAP] negative and egg negative) have increased systemic production of proinflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α) and decreased down-regulatory IL-10. A total of 804 children, 2-19 years of age, were surveyed between July and December 2009 and tested for S. haematobium, Plasmodium falciparum, filariasis, and soil-transmitted helminth infections. Plasma levels of IL-6, TNF-α, and IL-10 were compared for S. haematobium-positive and S. haematobium-negative children, adjusting for malaria, filaria, and hookworm co-infections, and for nutritional status, age group, sex, and geographic location. IL-10 was significantly elevated among children infected with S. haematobium, showing bimodal peaks in 7-8 and 13-14 years age groups. IL-10 was also higher among children who were acutely malnourished, whereas IL-10 levels were lower in the presence of S. haematobium-filaria co-infection. After adjustment for co-factors, IL-6 was significantly elevated among children of 5-6 years and among those with P. falciparum infection. Lower levels of IL-6 were found in malaria-hookworm co-infection. High levels of TNF-α were found in children aged 11-12 years regardless of infection status. In addition, village of residence was a strong predictor of IL-6 and IL-10 plasma levels. In adolescent children infected with S. haematobium, there is an associated elevation in circulating IL-10 that may reduce the risk of later morbidity. Although we did not find a direct link between S. haematobium infection and circulating pro-inflammatory IL-6 and TNF-α levels, future T-cell stimulation studies may provide more conclusive linkages between infection and cytokine responses in settings that are endemic for multiple parasites and multiple co-infections.

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“…It has been theorized that there may be a "point of no return" with regard to pulmonary vascular remodeling, after which treatment of the infection will not result in reversal of PAH, or will be associated with impaired healing, as described above. 2,91,92,95 It is unclear whether Sch-PH should be treated solely with S. mansoni chemotherapy, eradicating the parasite and therefore eliminating the etiologic factor, or with additional treatments geared toward PAH (e.g., prostanoids, endothelin receptor antagonists, or phosphodiesterase-5 [PDE-5] inhibitors; Table 2). 96 There are very few data regarding the use of these therapies in the setting of Sch-PH.…”

Section: Immunology Of Sch-phmentioning

confidence: 99%

Schistosomiasis‐Associated Pulmonary Hypertension

et al. 2014

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Schistosomiasis, a parasite-borne disease, is highly prevalent in Africa and Asia; it is estimated that close to 20 million people worldwide have a severe form of the disease. The chronic form can affect the gastrointestinal system and lead to hepatosplenic disease, and it may cause cardiopulmonary complications, including pulmonary hypertension. The exact pathogenesis of schistosomiasis-associated pulmonary hypertension (Sch-PH) remains unclear, although several mechanisms, including parasitic arterial embolization, pulmonary arteriopathy, and portopulmonary hypertension-like pathophysiology, have been suggested. The immunopathology of the disease is also unclear, although there are similarities with the immunology of idiopathic pulmonary arterial hypertension (PAH). Finally, the treatment of Sch-PH has not been well studied. There is some evidence on treating the underlying infection, with unclear effect on Sch-PH, and advanced PAH therapies are now being suggested, but more studies are needed to confirm their efficacy.

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Remodeling of hepatic vascular changes after specific chemotherapy of schistosomal periportal fibrosis

Cited by 24 publications

References 19 publications

Effect of Chemotherapy with Praziquantel on the Production of Cytokines and Morbidity Associated with Schistosomiasis Mansoni

Effect of Chemotherapy with Praziquantel on the Production of Cytokines and Morbidity Associated with Schistosomiasis Mansoni

Age-Stratified Profiles of Serum IL-6, IL-10, and TNF-α Cytokines Among Kenyan Children with Schistosoma haematobium, Plasmodium falciparum, and Other Chronic Parasitic Co-Infections

Schistosomiasis‐Associated Pulmonary Hypertension

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