l-Deprenyl Reverses Age-Associated Decline in Splenic Norepinephrine, Interleukin-2 and Interferon-γ Production in Old Female F344 Rats

• Published in: Neuroimmunomodulation 2013-01, Vol.20 (2), p.72-78
• Main Authors: ThyagaRajan, Srinivasan, Madden, Kelley S., Boehm, Gary W., Stevens, Suzanne Y., Felten, David L., Bellinger, Denise L.
• Format: Article
• Language: English
• Subjects: Aging - drug effects; Aging - immunology; Aging - metabolism; Animals; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Female; Immunity, Cellular - drug effects; Immunity, Cellular - immunology; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Neuroprotective Agents - pharmacology; Norepinephrine - biosynthesis; Original Paper; Rats; Rats, Inbred F344; Selegiline - pharmacology; Spleen - drug effects; Spleen - immunology; Spleen - metabolism; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - immunology
• ISSN: 1021-7401; 1423-0216
• DOI: 10.1159/000345043

Aging in female rats is associated with cessation of reproductive cycles, development of mammary cancer, and increased incidence of autoimmune diseases. Previously, we demonstrated an age-related decline in sympathetic noradrenergic (NA) innervation in the spleen and lymph nodes of female F344 rats accompanied by significantly reduced natural killer cell activity, interleukin (IL)-2 and interferon (IFN)-γ production, and T- and B-cell proliferation, suggesting possible links between sympathetic activity and immunosenescence. Objectives: The aim of this study is to investigate the effects of l -(–)-deprenyl, a monoamine oxidase-B inhibitor, on the sympathetic nervous system and cell-mediated immune responses in old female rats. Methods: Low doses of l -deprenyl (0.25 or 1.0 mg/kg body weight, BW) were administered intraperitoneally to 19- to 21-month-old female F344 rats for 8 weeks. To assess the stereoselectivity of the effects of deprenyl on splenic sympathetic activity and immune responses, the d -enantiomer ( d -(+)-deprenyl; 1.0 mg/kg BW) was also included in the studies. Norepinephrine (NE) concentration and content, and mitogen-induced T-cell proliferation and cytokine production were assessed in the splenocytes after deprenyl treatment. Results: Treatment with l -deprenyl reversed the age-related decrease in NE concentration and content and IFN-γ production, and increased IL-2 production in the spleen while d -deprenyl did not affect the age-associated reduction in splenic NE levels or cytokine production. Conclusions: These findings demonstrate that l -deprenyl exerts neurorestorative and immunostimulatory effects on the sympathetic nervous system and cell-mediated immune responses during aging and provides evidence for a causal relationship between some aspects of immunosenescence and the age-related decline in sympathetic nerves in the spleens of female F344 rats.