interleukin-8 and Chagas-Disease

The discovery and development of new drugs for the treatment of Chagas disease is urgent due to the high toxicity and low cure efficacy, mainly during the chronic phase of this disease. Other chemotherapeutic approaches for Chagas disease treatment are being researched and require screening assays suitable for evaluating the effectivity of new biologically active compounds. This study aims to evaluate a functional assay using the internalization of epimastigotes forms of Trypanosoma cruzi by human peripheral blood leukocytes from healthy volunteers and analyses by flow cytometry of cytotoxicity, anti-T. cruzi activity, and immunomodulatory effect of benznidazole, ravuconazole, and posaconazole. The culture supernatant was used to measure cytokines (IL-1-β, IL-6, INF-γ, TNF and IL-10) and chemokines (MCP-1/CCL2, CCL5/RANTES and CXCL8/IL-8). The data showed a reduction in the internalization of T. cruzi epimastigote forms treated with ravuconazole, demonstrating its potential anti-T. cruzi activity. In addition, an increased amount of IL-10 and TNF cytokines was observed in the supernatant of cultures upon the addition of the drug, mainly IL-10 in the presence of benznidazole, ravuconazole and posaconazole, and TNF in the presence of ravuconazole and posaconazole. Moreover, the results revealed a decrease in the MCP-1/CCL2 index in cultures in the presence of benznidazole, ravuconazole, and posaconazole. A decrease in the CCL5/RANTES and CXCL8/IL-8 index in cultures with BZ, when compared to the culture without drugs, was also observed. In conclusion, the innovative functional test proposed in this study may be a valuable tool as a confirmatory test for selecting promising compounds identified in prospecting programs for new drugs for Chagas disease treatment.

Topics: Chagas Disease; Cytokines; Flow Cytometry; Humans; Interleukin-10; Interleukin-8; Nitroimidazoles; Trypanocidal Agents; Trypanosoma cruzi

It is known that the immunoregulatory networks in human Chagas disease play a key role in parasitemia control during the acute phase. However, little is known regarding the control of parasitemia during the chronic phase. The aim of the study was to describe the serum cytokine profile of

Topics: Adult; Chagas Disease; Chronic Disease; DNA, Protozoan; Female; Humans; Interleukin-10; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Parasitemia; Polymerase Chain Reaction; Retrospective Studies; Young Adult

Trypanosoma cruzi metacyclic trypomastigotes (MT), but not blood form trypomastigotes (BFT), are highly mucosally infective. We investigated the abilities of MT and BFT to induce inflammation and/or intracellular killing activity within mucosal epithelia. BFT, but not MT, induced marked increases in interleukin-8, GRO-alpha, MCP-1, and nitric oxide production in HeLa and AGS cells, despite similar infectivities. MT may avoid induction of inflammation as an important biological mechanism facilitating mucosal invasion.

Topics: Animals; Cell Line; Chagas Disease; Chemokine CCL2; Chemokine CXCL1; Chemokines; Chemokines, CXC; Chemotactic Factors; HeLa Cells; Humans; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Interleukin-8; Mucous Membrane; Nitric Oxide; RNA, Messenger; Trypanosoma cruzi