Chronoimmunomodulation of melatonin on bactericidal activity of human blood phagocytes

摘要

In this work we studied the chronoimmunomodulation effect of melatonin on blood phagocytes. This cells stimulated with melatonin and incubated with EPEC presented enhanced superoxide. Mononuclear (MN) and polymorphonuclear (PMN) phagocytes stimulated with melatonin in the presence of bacteria showed enhanced superoxide release.EPEC killing by MN phagocytes stimulated with melatonin was time dependent. The highest bactericidal index were observed over the period of 60 and 120 minutes of incubation. PMN phagocytes stimulated with melatonin, independently of time, showed increased in the bactericidal activity. Interactions between melatonin and phagocytes support the hypothesis of pineal chronomodulation microbicidal processes. Introduction Several works have suggested that hormones and neuropeptides act as potent immunomodulators participating in various aspects of immune system function, both in health and disease (Dardenne & Savino,1994; Blalock 1994; Lissoni et.al, 1997; Srinivasan et al., 2005).The pineal gland, with its indole metabolism and particularly melatonin synthesis, is characterized by a series of oxidative processes involving photochemical reactions and redox reactions with the participation of free radicals or peroxides inhibitors or generators. Melatonin is an endogenous neurohormone and its actions are related to its capability to scavenge free radicals, increase the antioxidant activity of enzymes (Keplac et al, 2005; . Sudnikovich et al, 2007) mainly due to its scavenging capacity against reactive oxygen species (Keplac et al, 2005). These observations have led to the hypothesis of pineal involvement in the body oxidative processes (Ian?s, et al., 1991). Some works have reported a functional connection between the pineal gland and the immune system (Liebmann et al., 1997; Pandi-Perumal et al, 2008). The pineal hormone melatonin due to its lipophilic nature, has access to every cell and every part of a cell in the body, suggesting that it could exert effects on blood immune cells. Probably the effects of melatonin on the immune cells, may be by indirect influence on the synthesis and release the other hormones or cytokine or by direct action on phagocytosis and phagocytic bichemical process (Liebmann et al., 1997; Rodriguez et al., 1999). Enteropathogenic Escherichia coli (EPEC) is a bacterium that causes diarrhea in infants in developing countries (Gomes et al., 1991; Kosek et al, 2003). Studies have demonstrated that blood phagocytes present activation of oxidative metabolism and bactericidal activity when incubated with this bacteria, an activity that may be modulated by some factors present in the serum ( Honorio-Fran?a et al., 1997; Honorio-Fran?a et al, 2001).The bactericidal activity is probably due to the activation of superoxide anion-dependent killing mechanism operating on the cell surface (Asad, 1994). There is considerable evidence that phagocytes rapidly increase oxygen consumption during phagocytosis or upon stimulation of their with a variety of agents (Badwey, et al, 1983). The products of oxygen reduction and excitation have been implicated in the destruction of bacteria, yeast, viruses and mycoplasmas by phagocytes, constituting key components in the microbicidal mechanisms of phagocytes (Babior, 1984; Badwey, et al, 1983; Honorio-Fran?a, et al, 1997).Some studies have shown that melatonin has an antioxidant effect which includes the scavenging of highly reactive oxygen free radicals and there is evidence that melatonin may protect the effects of free radical-induced neuronal damage (Sandyk, 1990; Reiter,1993; Tan, 1994; Rodriguez et al., 1999; Keplac et al, 2005; . Sudnikovich et al, 2007)., whereas others demonstrated a prooxidant effect (Ian?s, et al., 1991) and probably acts amplifying cellular activation reactions (Fjaerli et al., 1999). In the present study we investigated the chronoimmunomodulation effect of melatonin on superoxide release and the bactericidal activity by blood phagoc