Low IL-6, IL-10, and TNF-α and High IL-13 Cytokine Levels Are Associated with Severe Hepatic Fibrosis in Schistosoma mansoni Chronically Exposed Individuals.

Mable M Mutengo,James C L Mwansa,Paul Kelly,Patrick Musonda,Geoffrey Kwenda,James Chipeta,Takafira Mduluza

doi:10.1155/2018/9754060

Abstract

Several studies have attributed the etiopathogenesis of chronic Schistosoma mansoni related hepatic fibrosis to unregulated immune responses against trapped parasite ova in the host. However, there is limited data on immune profiles associated with varying degrees of the disease in a population under chronic exposure to the parasite. We therefore investigated the role of selected T-helper (Th)1, Th2, and Th17 cytokines in relation to hepatic fibrosis severity among individuals resident in a hyper-Schistosoma mansoni endemic region of Western Zambia. Two hundred and forty-four S. mansoni infected individuals with and without fibrosis were analysed for cytokine profiles. Based on hepatic fibrosis stage as determined by ultrasound, participants were categorized into Group 0, Group I, Group II, and Group III. Cytokines were measured in S. mansoni egg stimulated whole blood culture supernatants using the BD Cytometric Bead Array kits. Compared to the nonfibrotic group, participants in the severe hepatic fibrotic group produced less interleukin- (IL-) 6, IL-10, and tumour necrosis factor-alpha (TNF-α). On the other hand, IL-13 was significantly elevated in this group compared to the nonfibrotic group (p < 0.001). Our results suggest that low IL-6, IL-10, and TNF-α and high IL-13 levels may influence S. mansoni disease progression.

Highlights

In endemic areas, Schistosoma mansoni disease presentations are often subtle and unrecognized
While it has been previously reported that Th1 immune responses are associated with acute infection [5], studies are suggesting that Th1 cytokines such as IFN-γ and TNF-α could be involved in regulating hepatic fibrosis observed in chronic schistosomiasis disease
We further demonstrate for the first time the possible protective role of IL-6 against severe hepatic fibrosis in a population chronically exposed to S. mansoni parasites

Summary

Introduction

Schistosoma mansoni disease presentations are often subtle and unrecognized. In a subset of infected individuals, severe hepatic fibrosis occurs due to excessive deposition of extracellular matrices in portal spaces in response to trapped Schistosoma egg leading to presinusoidal fibrosis and portal hypertension [1, 2]. While it has been previously reported that Th1 immune responses are associated with acute infection [5], studies are suggesting that Th1 cytokines such as IFN-γ and TNF-α could be involved in regulating hepatic fibrosis observed in chronic schistosomiasis disease. IFN-γ inhibits the synthesis of extracellular molecules by the hepatic stellate cells [11, 14] and enhances matrix metalloprotease (MMP) gene expression [15] Low levels of this cytokine are reported to be associated with severe periportal fibrosis in S. mansoni infected people [2]. We report findings on the role of selected Th1, Th2, Th17, and regulatory cytokines in individuals with varying stages of hepatic fibrosis in the same population

Materials and Methods

Results

Discussion

Conclusion

Conflicts of Interest