IL‐10 Plays a Role in the Modulation of Human Granulomatous Hypersensitivity Against Schistosoma mansoni Eggs Induced by Immune Complexes

Abstract

Rezende SA, Silva-Teixeira DN, Drummond SC, Goes AM. IL-10 Plays a Role in the Modulation of Human Granulomatous Hypersensitivity Against Schistosoma mansoni Eggs Induced by Immune Complexes. Scand J Immunol 1997;46:96-102 It has been demonstrated that the chronic intestinal form of schistosomiasis is associated with the establishment and maintenance of a variety of immunoregulatory mechanisms that lead to a diminished granulomatous reaction to parasite eggs. Using an in vitro model of granuloma reaction we showed that immune complexes (IC) isolated from the sera of chronic intestinal schistosomiasis patients were able to reduce the granulomatous hypersensitivity (developed by peripheral blood mononuclear cells (PBMC) from schistosomiasis patients) to soluble egg antigen (SEA)-conjugated polyacrylamide beads (PB-SEA). This inhibitory activity, mediated by IC, was also observed in the proliferative response of PBMC stimulated with SEA and soluble worm antigen preparation (SWAP). Furthermore, we observed a decrease in TNF-a and an increase in IL-10 production by PBMC treated with IC in an in vitro granuloma reaction. This phenomenon was also seen in a cell proliferation assay when PBMC were treated with IC and stimulated with S. mansoni antigens. These results demonstrate that circulating IC may down-regulate PBMC reactivity to S. mansoni antigens by changing the cytokine pattern produced by these cells.

Cytokine secretion profile associated with periportal fibrosis in S. mansoni-infected Egyptian patients

“…A stronger PBMC proliferation against SAWA than SEA was demonstrated. This is in agreement with several reports of a lower response to SEA in comparison with SWAP in chronic schistosomiasis (Freeman et al 1983;Colley et al 1986;Roberts et al 1993;Viana et al 1994;Bahia-Oliveira et al 1996;Rezende et al 1997). It has been suggested that the lower proliferative response against SEA observed in the chronic phase of the disease is due to modulation of the cellular response against eggs with the progression of the infection .…”

“…Adult worms induce a Th1-type cytokine profile with elevated levels of IFN-γ, IL-12, and TNF-α (Grzych et al 1991;Leptak and McKerrow 1997). In accordance with our results, Rezende et al (1997) observed an elevation of TNF-α in in vitro granuloma formation and cell proliferation assays when PBMC from chronic INT patients were stimulated with S. mansoni egg antigens. In contrast, high levels of TNF-α were found in the circulation of patients with hepatosplenic schistosomiasis (Zwingenberger et al 1990;Mwatha et al 1998).…”

Regulation of Granulomatous Inflammation in Experimental Models of Schistosomiasis

“…Table 2 shows the effects on HG size of introduction during infection of blocking antibodies to some cytokines and cytokine receptors. By this criterion, IL-2 (22), TNF-␣ (71), and the IFN-␥ receptor (119) in S. mansoni-infected mice and IL-5 (28) and the IL-2 receptor (27) in S. japonicum-infected mice participated in HG pathogenesis. In S. mansoni-infected mice IL-2 (22), IL-5 (125), IL-10 (15, 40), IFN-␥ (125), and the IFN-␥ receptor (119) and in S. japonicum-infected animals the IL-2 receptor (27) were also involved in determining the cellular composition of the HG.…”

“…By this criterion, IL-2 (22), TNF-␣ (71), and the IFN-␥ receptor (119) in S. mansoni-infected mice and IL-5 (28) and the IL-2 receptor (27) in S. japonicum-infected mice participated in HG pathogenesis. In S. mansoni-infected mice IL-2 (22), IL-5 (125), IL-10 (15, 40), IFN-␥ (125), and the IFN-␥ receptor (119) and in S. japonicum-infected animals the IL-2 receptor (27) were also involved in determining the cellular composition of the HG. Table 3 shows that the introduction during infection of some recombinant cytokines, including recombinant IL-2 (91), recombinant IL-7 (146), and recombinant TNF-␣ (3, 71), enhanced HG size.…”

Immunological and parasitological parameters after treatment with dexamethasone in murine Schistosoma mansoni

“…Furthermore, an opposite effect was seen in IL-10-deficient mice . Rezende et al (1997) suggested that immunocomplexes from patients with chronic intestinal schistosomiasis are able to modulate granulomatous hypersensitivity to S. mansoni eggs by inducing prostaglandin E production that augments IL-10 levels. Cytokines are believed to modulate the amount of fibrosis and granuloma size and to play a fundamental role in the pathology of schistosome infection.…”