Trends in Immunology
Volume 24, Issue 8, August 2003, Pages 438-443
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Lymphocytes transport serotonin and dopamine: agony or ecstasy?

https://doi.org/10.1016/S1471-4906(03)00176-5Get rights and content

Abstract

Lymphocytes apparently carry active transport systems for the neurotransmitters serotonin and dopamine. Meanwhile, pharmacological substrates for the transporters have been claimed to impinge on immune function: these include, commonly used antidepressants [such as fluoxetine (Prozac®)], appetite suppressants and the recreational drugs MDMA [3,4-Methylenedioxymethamphetamine (‘Ecstasy’)] and cocaine. Data on these issues can be patchy. Given the widespread use – or, abuse – of these drugs, we propose that a concerted effort should be made towards a full description of biogenic amine transporters in the immune system and the potential impact of their substrates – both natural and artificial – on its functioning. Could such knowledge one day help to treat immune deficiency and/or dysregulation?

Section snippets

Evidence that lymphocytes carry transporters for serotonin and dopamine

Some relevant pharmacological characteristics of the transporters involved in active uptake of serotonin, dopamine, and noradrenaline are outlined in Table 1. Outside the brain, the most widely described of these is the serotonin transporter (SERT) in platelets.

Impact on immune function of drugs that target biogenic monoamine transporters

Here, we concisely review some of the literature pertaining to how psychotropic drugs and antidepressants that target the monoamine transporters might perturb the proper functioning of the immune system.

Is drug-induced immune disturbance mediated through lymphocyte monoamine transporters?

he existence of bi-directional communication among the immune, neuroendocrine and central nervous systems is beyond dispute, even if current insight probably represents just the tip of an iceberg 36, 37. Stress clearly perturbs immune function, as does mood and emotion. Main players mooted responsible for such crosstalk between mind and body are the sympathetic nervous system and the hyopthalmus–pituitary–adrenal (HPA) axis. Thus, with investigations in vivo, it becomes difficult to untangle

Transports of delight?

In this Review we have posed the following questions: (1) do lymphocytes express functional transporters for serotonin and catecholamines; (2) do drugs in widespread use that target these structures disturb immune behaviour; and (3) are such effects dependent on direct modulation of lymphocyte-associated transporter activity? Although there appears to be sufficient (although still far from complete) evidence to answer affirmatively to the first question there remains confusion and/or simple

Acknowledgements

We are indebted to the many who have helped construct this Review. Space constraints limit us mentioning you by name as it does our ability to cite all the references pertinent to this Review. The work of J.G. is supported by the Medical Research Council (UK) and that of N.M.B by the Wellcome Trust. J.G. is a non-Clinical MRC Research Professor.

References (55)

  • R.V. House

    Selective modulation of immune function resulting from in vitro exposure to methylenedioxymethamphetamine (Ecstasy)

    Toxicology

    (1995)
  • T.J. Connor

    Acute 3,4-methylenedioxymethamphetamine (MDMA) administration produces a rapid and sustained suppression of immune function in the rat

    Immunopharmacology

    (1998)
  • T.J. Connor

    Methylenedioxymethamphetamine (MDMA; ecstasy) suppresses IL-1β and TNF-α secretion following an in vivo lipopolysaccharide challenge

    Life Sci.

    (2000)
  • T.J. Connor

    Methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) suppresses antigen specific IgG2a and IFN-γ production

    Immunol. Lett.

    (2001)
  • R. Pacifici

    Effects of repeated doses of MDMA (‘ecstasy’) on cell-mediated immune response in humans

    Life Sci.

    (2001)
  • T.J. Connor

    An assessment of the acute effects of the serotonin releasers methylenedioxymethamphetamine, methylenedioxyamphetamine and fenfluramine on immunity in rats

    Immunopharmacology

    (2000)
  • J. Clancy

    Effects of subchronic d-fenfluramine on splenic immune functions in young and old male and female Fischer 344 rats

    Int. J. Immunopharmacol.

    (1991)
  • G.C. Baldwin

    Acute and chronic effects of cocaine on the immune system and the possible link to AIDS

    J. Neuroimmunol.

    (1998)
  • T. Pellegrino et al.

    In vivo effects of cocaine on immune cell function

    J. Neuroimmunol.

    (1998)
  • V.A. Edgar

    Fluoxetine action on murine T-lymphocyte proliferation: participation of PKC activation and calcium mobilisation

    Cell. Signal.

    (1998)
  • A.M. Genaro

    Differential effects of fluoxetine on murine B-cell proliferation depending on the biochemical pathways triggered by distinct mitogens

    Biochem. Pharmacol.

    (2000)
  • C.M. Helgason

    The effects of St. John's Wort (Hypericum perforatum) on NK cell activity in vitro

    Immunopharmacology

    (2000)
  • A. Serafeim et al.

    The immune system gets nervous

    Curr. Opin. Pharmacol.

    (2001)
  • A. Serafeim

    Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells

    Blood

    (2003)
  • T.J. Connor

    Methylenedioxymethamphetamine-induced suppression of interleukin-1β and tumour necrosis factor-α is not mediated by serotonin

    Eur. J. Pharmacol.

    (2001)
  • W. Xu

    Cocaine effects on immunocompetent cells: an observation of in vitro cocaine exposure

    Int. J. Immunopharmacol.

    (1999)
  • H. Mathews

    Effect of d-fenfluramine on the lymphocyte response of HIV+ humans

    Int. J. Immunopharmacol.

    (1998)
  • Cited by (0)

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