Modulation of superoxide anion levels of macrophages from young-adult and old mice by the norepinephrine metabolite, 4-hydroxy-3-methoxyphenyl-glycol.

It is well known that a bidirectional relation exists between the immune and the classic animal regulation systems, the nervous and endocrine systems. It has also been reported that ageing has a negative effect on neuro-immuno-endocrine integration. Since it has been shown that norepinephrine (NE) differently modulates the phagocytic process of macrophages from young or old mice, and considering that NE has a short lifetime, the aim of this study is to evaluate the possible immunomodulatory role of the NE end-metabolite, 4-hydroxy-3-methoxyphenyl-glycol (HMP-glycol), on the superoxide anion levels of peritoneal macrophages from young-adult (22+/-2 weeks) and old (72+/-2 weeks) BALB/c mice. Macrophages were incubated with HMP-glycol in a range of concentrations between 10(-12) and 10(-3)M, and superoxide anion levels (both extracellular and intracellular) were evaluated by using the NBT reduction test. The response of macrophages to HMP-glycol was different between young-adult and old animals. While all concentrations (10(-12), 10(-9), 10(-7), 10(-5), 10(-3)M) of HMP-glycol led to lower extracellular O(-)(2) levels (p<0.05) in macrophages from young-adult mice, only the 10(-3)M concentration of HMP-glycol led to a significant decrease in the extracellular O(-)(2) production in macrophages from old mice. No significant changes were found in the intracellular O(2)(-) levels when macrophages were incubated with the different concentrations of HMP-glycol in either young-adult or old mice. Thus, the modulation of macrophage function by NE not only depends on their concentration, but also on the products of NE catabolism. The effect of NE metabolite will also depend on the age of the animals as there is an age-dependent decreased capacity to respond to low concentrations of HMP-glycol.