The release of sympathetic neurotransmitters is impaired in aged rats after an inflammatory stimulus: a possible link between cytokine production and sympathetic transmission.
Aging results in a general decline in the response to external insults, including acute inflammatory challenges. In young animals, the inflammatory response requires activation of the sympathetic system, including neurotransmitters such as ATP, and catecholamines (epinephrine and norepinephrine). To test whether aging affects activation of this axis, and whether this in turn might affect cytokine release, we administered lipopolysaccharide (LPS) i.p. to adult, middle-aged and aged Fisher 344 rats (6-, 15- and 23-month old, respectively) and evaluated the early (0-12h) serum levels of Neuropeptide-Y (NP-Y), ATP and vanillyl mandelic acid (VMA, as an indirect measurement of catecholamine levels). In addition, we evaluated the association between these factors and serum levels of the cytokines tumor necrosis factor-alpha (TNFalpha) and interleukin-10 (IL-10). Induction of both ATP and NP-Y was markedly reduced in the serum of aged animals, when compared to their younger counterparts, while induction of VMA was not affected by age. In spite of these changes, serum levels of TNFalpha and IL-10 were strongly hyper induced and delayed in aged rats. The results suggest that during aging there is a dysregulation in sympathetic neurotransmitter regulatory mechanisms, and this might play a role in the impairment of the inflammatory response.
Donoso
Verónica
V
Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile.
Gomez
Christian R
CR
Orriantia
Miguel Angel
MA
Pérez
Viviana
V
Torres
Claudio
C
Coddou
Claudio
C
Nelson
Pablo
P
Maisey
Kevin
K
Morales
Bernardo
B
Fernandez
Ricardo
R
Imarai
Mónica
M
Huidobro-Toro
Juan Pablo
JP
Sierra
Felipe
F
Acuña-Castillo
Claudio
C
D000255:Adenosine Triphosphate / Q000097:blood; D000375:Aging / Q000276:immunology* / Q000502:physiology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology*; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008959:Models, Neurological; D015213:Neuroimmunomodulation; D009478:Neuropeptide Y / Q000097:blood; D018377:Neurotransmitter Agents / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013564:Sympathetic Nervous System / Q000378:metabolism; D009435:Synaptic Transmission; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014642:Vanilmandelic Acid / Q000097:blood
D016207:Cytokines; D008070:Lipopolysaccharides; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014642:Vanilmandelic Acid; D000255:Adenosine Triphosphate