Ação do fator de necrose tumoral-alfa adsorvido em microesfera de polietilenoglicol sobre a atividade funcional de monócitos do sangue periférico humano

Abstract

The therapeutic improvement of immunotherapeutics through their incorporation into microcarriers is an important strategy for immunomodulating the immune system. Among immunotherapeutics, cytokines represent a viable alternative for several infectious diseases. In this sense, tumor necrosis factor-alpha (TNF-α) is a cytokine that plays an important role in inflammatory and infectious processes, however little is known about its effects when associated with microcarriers. Thus, the objective of this work was to analyze the immunomodulatory effect of TNF-α adsorbed on polyethylene glycol (PEG) microspheres on the functional activity of human peripheral blood phagocytes in the presence of enteropathogenic Escherichia coli (EPEC). The microspheres were produced from polyethylene glycol (PEG) 6000 and sodium sulfate in aqueous solution, by a thermally induced phase separation process. The adsorption of TNF-α to the microspheres was carried out by incubation (v/v) at 37 °C for 30 minutes. Blood samples from healthy donors were obtained to perform biological tests. Rheological parameters were evaluated in whole blood. Cell viability, phagocytosis index, microbicidal activity, release of superoxide anion (O₂⁻) and concentration of superoxide dismutase (SOD) in mononuclear cells in the presence or absence of enteropathogenic Escherichia coli (EPEC) were also evaluated. It was observed that, regardless of the presence of TNF-α adsorbed or not on the PEG microsphere, there were no differences in blood flow and viscosity (p>0.5). The phagocytosis index and microbicidal activity were also similar between treatments. Superoxide anion was higher when MN cells were treated with TNF-α adsorbed to the PEG microsphere. There were no differences in the concentration of superoxide dismutase (SOD) in MN cell culture supernatant. These data suggest that TNF-α adsorbed to the PEG microsphere increased cellular oxidative stress and could act as a functional material capable of activating pro-oxidative cellular mechanisms.