Anti-tumor effect of L-deprenyl is associated with enhanced central and peripheral neurotransmission and immune reactivity in rats with carcinogen-induced mammary tumors

J Neuroimmunol. 2000 Sep 22;109(2):95-104. doi: 10.1016/s0165-5728(00)00305-2.

Abstract

L-Deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, has previously been shown to improve immune responses and restore noradrenergic (NA) nerve fibers in the spleen of old rats. In tumor-bearing rats, L-deprenyl inhibited tumor incidence and enhanced tuberoinfundibular dopaminergic (TIDA) neurotransmission in the hypothalamus. The aim of the present study was to investigate whether alterations in sympathetic NA activity and cellular immune responses in the spleen, and TIDA activity in the hypothalamus, accompany deprenyl-induced regression of 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced mammary tumors. Rats with DMBA-induced mammary tumors were treated with 0, 2.5 mg, or 5.0 mg/kg body weight of deprenyl daily for 13 weeks. Saline-treated tumor-bearing rats exhibited reduced splenic IL-2 and IFN-gamma levels, and lowered splenic norepinephrine (NE) concentration and hypothalamic dopaminergic activity, compared to rats without tumors. In contrast, treatment with 2.5 mg/kg and 5.0 mg/kg of deprenyl reduced the number and size of mammary tumors. Deprenyl-induced tumor regression was accompanied by increased immune measures in the spleen, including enhanced IL-2 and IFN-gamma production, and NK cell activity. Neural measures enhanced by deprenyl included NE concentration in the spleen and TIDA neuronal activity in the hypothalamus. These results suggest that (1) mammary tumorigenesis is associated with the inhibition of sympathetic NA activity in the spleen, TIDA activity in the hypothalamus, and cell-mediated immunity, and (2) reversal of the inhibition of catecholaminergic neuronal activities of the central nervous system and peripheral nervous system by deprenyl may enhance anti-tumor immunity.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Carcinogens
  • Cell Division / immunology
  • Female
  • Flow Cytometry
  • Hydroxyindoleacetic Acid / metabolism
  • Immune System / drug effects
  • Immune System / immunology
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Killer Cells, Natural / immunology
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / immunology*
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Neuroimmunomodulation / drug effects*
  • Neuroimmunomodulation / immunology
  • Norepinephrine / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Selegiline / pharmacology*
  • Serotonin / metabolism
  • Spleen / cytology
  • Spleen / immunology
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / immunology
  • Synaptic Transmission / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Carcinogens
  • Interleukin-2
  • Monoamine Oxidase Inhibitors
  • 3,4-Dihydroxyphenylacetic Acid
  • Selegiline
  • Serotonin
  • Hydroxyindoleacetic Acid
  • 9,10-Dimethyl-1,2-benzanthracene
  • Interferon-gamma
  • Norepinephrine