The influence of the selective
serotonin (5-HT) reuptake inhibiting
antidepressant zimeldine and its metabolite
norzimeldine was tested on
experimental allergic neuritis (EAN) in Lewis rats, which is an animal model of the
Guillain-Barré syndrome (GBS) in man.
Zimeldine and
norzimeldine both suppressed clinical signs of actively induced EAN when given at a dose of 20 mg/kg/day intraperitoneally via osmotic pumps. The effects of
zimeldine, its metabolites
norzimeldine and
CPP 200 as well as of the
antidepressants clomipramine,
imipramine and
maprotiline on in vitro immune response were tested. Thereby we used an immunospot assay for
interferon-gamma (IFN-gamma) produced by lymph node mononuclear cells (MNC), which reflects number of memory T lymphocytes activated by
antigen or
lectin, in this experiment bovine peripheral nerve myelin (BPM) and
phytohemagglutinin (PHA), respectively. In the IFN-gamma secretion assay
zimeldine,
CPP 200,
clomipramine and
maprotiline all in a concentration-dependent mode reduced the number of IFN-gamma secreting cells while
norzimeldine and
imipramine did not affect the IFN-gamma secretion. In assays for proliferation in response to
antigen or
lectin, the concentration 10(-4) M was judged toxic for all substances tested, and at concentrations below that all but
zimeldine showed a dose-dependent slight reduction of MNC proliferation. The action of several drugs on induced T cell secretion of IFN-gamma suggests that the mechanisms for the suppressive effect of
zimeldine and
norzimeldine on EAN symptoms can be due to an action on myelin T cell autoreactivity. All the monoamine reuptake inhibiting
antidepressants tested in this study showed immunomodulatory effects by either a reduction of the number of IFN-gamma-secreting cells or the MNC proliferation. These observations call for further studies of immunological mechanisms in the pathogenesis of
mental disorders as well as on the potential role of drugs acting on the monoamine systems in the treatment of recognized
autoimmune diseases.