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Using Eggs from Schistosoma mansoni as an In vivo Model of Helminth-induced Lung Inflammation
Published on: June 5, 2012
Effect of interferon-alpha on experimental Schistosoma mansoni infection in mice
Amany A Abd El-Aal1, Maha H El-Arousy, Raga'a Issa
1Department of Parasitology, Faculty of Medicine, Cairo University, Egypt.
Abstract:
To investigate the immunomodulatory effect of the Th1 mediated cytokine IFN-alpha on schistosomiasis, this cytokine was weekly injected into mice experimentally infected with S. mansoni, beginning from day 0 (group II), week 3 (group III), week 6 (group IV) and week 10 (group V) post-infection. TGF-beta1 serum levels were estimated on a weekly basis and beginning one week after initiation of IFN-alpha therapy, while all animals were sacrified on week 14 to be used for egg counts in liver and small intestine, oogram study for determination of the maturity of deposited eggs, and histopathological examination of stained liver sections. IFN-alpha treated groups were characterized by a more intense oviposition in the intestine (liver/intestine ratio less than 1), with higher egg numbers the earlier IFN-alpha was administered. Oograms of the intestine indicated the level of immature eggs to be statistically significantly higher in group II, III and IV than in the control group I (p < 0.05). In IFN-alpha medicated mice, the mean numbers and diameters of hepatic granulomas were less than in GI, in addition to a lower representation of fibrocellular and fibrous granulomas among them (all parameters p < 0.05), especially in Gs IV & V. The inflammatory cell population in the form of eosinophils, histiocytes and giant cells was more pronounced in Gs III, IV & V. TGF-beta1 serum levels showed a progressive rise, however more pronounced in the untreated control. A statistically positive significant was established between TGF-beta1 levels and number, size and percentage of fibrotic hepatic granulomas in all groups.
Insights
Interferon-alpha (IFN-alpha) therapy in schistosomiasis-infected mice reduced hepatic granulomas and modulated egg deposition. Early IFN-alpha administration showed greater efficacy in controlling disease pathology.
Area of Science:
- Immunology
- Parasitology
- Hepatology
Background:
- Schistosomiasis is a parasitic disease with significant immunopathological consequences.
- The role of Th1-mediated cytokines like interferon-alpha (IFN-alpha) in modulating schistosomiasis is not fully understood.
- Hepatic granuloma formation and fibrosis are key pathological features of schistosomiasis.
Purpose of the Study:
- To investigate the immunomodulatory effects of IFN-alpha on experimental schistosomiasis.
- To determine the impact of IFN-alpha therapy timing on parasite egg burden and host immune response.
- To assess the influence of IFN-alpha on TGF-beta1 serum levels and hepatic granuloma characteristics.
Main Methods:
- Mice infected with Schistosoma mansoni were treated with weekly IFN-alpha injections at different time points post-infection.
- Serum TGF-beta1 levels were monitored weekly.
- Animals were sacrificed for egg counts, oogram analysis, and histopathological examination of liver tissues.
Main Results:
- IFN-alpha treatment led to increased intestinal egg deposition and a higher proportion of immature eggs.
- Reduced hepatic granuloma size, number, and fibrosis were observed in IFN-alpha treated groups, particularly with earlier treatment.
- Increased inflammatory cell infiltration (eosinophils, histiocytes, giant cells) was noted in later treatment groups.
- TGF-beta1 levels rose progressively but were higher in untreated controls, with a positive correlation between TGF-beta1 and hepatic fibrosis.
Conclusions:
- IFN-alpha exhibits immunomodulatory effects in schistosomiasis, influencing both parasite egg distribution and host liver pathology.
- Early administration of IFN-alpha appears more effective in mitigating hepatic granuloma formation and fibrosis.
- The interplay between IFN-alpha, TGF-beta1, and granuloma development warrants further investigation for therapeutic strategies.
