Interleucina - 4 recombinante como possível alvo para o tratamento da depressão

Abstract

Interleukin-4 (IL-4) is a cytokine with anti-inflammatory activity capable of reducing the effects of systemic and central inflammation in the body. Pro and anti-inflammatory cytokines are present in inflammatory responses induced by pathogens or changes caused by stress through physical and psychological stimuli. Stress is one of the main factors that lead to the onset of inflammatory responses, through the release of damage-associated molecular pattern (DAMPs). These changes are used to explain the development and progression of depression, which affects about 322 million people worldwide. In this dissertation, IL-4 was used to evaluate its effect on depressive-like behavior induced by the chronic unpredictable mild stress induction model (CUMS), in swiss mice. The mice submitted to CUMS showed a depressive-like behavior in the tail suspension tests (TST) and splash test (ST), as well as physiological changes, such as the increase in reactive species (RS), lipid peroxidation and changes in the activities of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) in prefrontal cortices, hippocampi and plasma. At the molecular level, changes occurred in the expression of cytokines such as IL- 1β, IL-4 and changes in the expression of NRF2, NF-kB, BDNF and changes in IDO activity in the prefrontal cortices and hippocampi. The treatment performed was to administer a single dose of IL-4 intranasally at a dose of 1ng / mouse (5 µL), which had an antidepressant-like effect on TSC and TS and influenced the modulation of oxidative stress and decreased neuroinflammation. These changes were confirmed by the decrease in ER, lipid peroxidation, and normalization of the activity of CAT and SOD enzymes in the prefrontal cortex, hippocampus and plasma. The decrease in the concentration of corticosterone in plasma and the normalization of expression of IL-1β, IL-4, NRF2, NF-kB, DBNF and IDO activity in prefrontal cortex and hippocampus also prove the activity of IL-4 in neuroinflammation in mice. These data suggest that the ability of IL-4 to reverse the depressive-like behavior in mice is promising for use in the treatment of depressive symptoms.