Association of Type 2 Cytokines with Hepatic Fibrosis in HumanSchistosoma mansoniInfection

Abstract

The objective of this study was to evaluate the role of cytokines in hepatic fibrosis in the prehepatosplenic and early hepatosplenic stages of schistosomiasis mansoni. Hepatic fibrosis was classified by ultrasonography of 94 patients. Immunological evaluation was performed by the measurement of secreted cytokines (interleukin-5 [IL-5], IL-10, IL-13, gamma interferon, tumor necrosis factor alpha, and transforming growth factor ␤) in peripheral blood mononuclear cells (PBMC) stimulated by Schistosoma mansoni antigens. Significantly, higher levels of IL-5, IL-10, and IL-13 were found in supernatants of soluble egg antigen-stimulated PBMC from subjects with degree III hepatic fibrosis compared to patients with degree I or II fibrosis. Significant increases in IL-5 and IL-13 levels were also observed in some of the subjects who remained untreated for 1 year following initial assessment and developed more serious fibrosis during this period. The data suggest a role for type 2 cytokines in hepatic fibrosis in human schistosomiasis mansoni.

Cytokine Production Associated with Periportal Fibrosis during Chronic Schistosomiasis Mansoni in Humans

“…This suggests that while intensity of infection may be sufficient to trigger the process of fibrosis, it is apparently not necessary for progression to severe fibrosis, a process that clearly depends on a number of other important factors. The intensities of infection and degrees of fibrosis apparently fluctuate considerably between different studies, and this may explain why a positive association between them has been found in some investigations (29) but not in others (4,33). In the present work, it is shown that parameters including age, gender, and intensity of infection are confounders, and all must be considered in order to establish potential associations between the production of cytokines and periportal fibrosis.…”

“…Moreover, increased levels of IL-13 were observed in PBMC that had been stimulated by SEA but not in those stimulated by SWAP, indicating that the response was primarily directed towards egg antigens. An important role for IL-13 in the development of liver fibrosis in mice and in humans has been pointed out by a number of investigators (4,7,8,9,13,33). It is known that IL-13 promotes collagen production through at least three distinct, but overlapping, mechanisms (for a review 33), and the expression in mice of the decoy receptor IL-13Ra2, which blocks IL-13 function, has been shown to also curtail hepatic fibrosis (9,23).…”

“…Given that IFN-␥ has been specifically associated with protection against fibrosis (4,11,17) and that its production depends on the relative concentration of IL-10, it is conceivable that IL-10 might also play some role in the development of morbidity in schistosomiasis. Furthermore, other cytokines, including IL-13, have already been reported to be involved in the development of periportal fibrosis in patients with chronic schistosomiasis living in areas of endemicity (4,27,31,33).…”

Cytokine profile associated with chronic and acute human schistosomiasis mansoni

“…7: box plot quartiles and medians of the log total IgE (A) and eosinophil levels (B) from patients with acute and chronic (HI: hepatointestinal; HS: hepatosplenic: IN: intestinal) schistosomiasis. Significant differences was considered when p < 0.05. cases of severe portal fibrosis were shown to be associated with low levels of IFN-γ and high levels of TNF-α (Henri et al 2002, Booth et al 2004, Ribeiro de Jesus et al 2004). Interestingly, IFN-γ produced following SEA or SWAP antigen stimulation gradually increased and correlated with the severity of the chronic clinical form.…”

“…However, other authors suggested that IL-13 levels tend to be higher during the pre-fibrosis phase and can function as an intermittent inducer of fibrosis (Morais et al 2002, Ribeiro de Jesus et al 2004.…”