antidepressants and immune system

[Guest guest]

It may be necessary to put a child with Lyme disease (or possible infectious stew whatever) on an antidepressant. I thought I remembered Dr. Nicholson writing that antidepressants suppress the immune system. So I tried to read the following abstracts. I am having trouble translating them into "good" or "bad." I'm pretty sure I got "bad" from the last article about tricyclics, but as for the rest, I can't remember about TNF-greek-letter and interleukin-number and what order things happen in. I just don't have a long-term memory for these things, I guess! I would have to look them all up all over again. So if anybody has any clues that will save me a few hours, fire away!- Kate1: J Infect. 2004 Aug;49(2):88-93.The immunostimulating and antimicrobial properties of lithium and antidepressants.Lieb J. 22 Rimmon Road, Woodbridge, CT 06525, USA. julianlieb@...     Eicosanoids are products of arachidonic acid (AA), an essential fatty acid. They include prostaglandins (PGs), prostacyclin (PGI2), thromboxanes (TXs), leukotrienes (LTs) and hydroxy fatty acids. AA is derived enzymatically from membrane phospholipids and to a lesser extent the diet. Eicosanoids self-regulate every cell, including those synthesizing serotonin, norepinephrine and dopamine and those subserving immune function, such as T-cells, B-cells, natural killer cells, macrophages, monocytes and dendritic cells. There is objective evidence that prostaglandins regulate the physiology of the hypothalamic-pituitary-adrenal axis (HPA). Elucidation of the structure and metabolic pathways of eicosanoids galvanized researchers into illuminating their role in physiology, pathology and pharmacology. Striking contradictions arose: eicosanoids were shown to activate and suppress microorganisms, potentiate and suppress immunity and possess pro- and anticancer properties. As prostaglandins are the most heavily studied eicosanoids in the context of mood and immunity I will focus on them in this article. I will present evidence of the immunostimulating and antimicrobial properties of lithium and antidepressants and propose that these properties are linked to the antiprostaglandin actions of these compounds.     PMID: 15236914 [PubMed - indexed for MEDLINE] 1: Psychiatry Res. 2005 Apr 30;134(3):251-8.Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor alpha and interleukin-6.Kubera M, Maes M, Kenis G, Kim YK, Lason W.Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Krakow, Poland. Kubera@...     Serotonin (5-HT) is a neurotransmitter and immune modulator. The effect of 5-HT on the production of cytokines by human macrophages and lymphocytes is poorly recognized. In the present article we examine the role of 5-HT in modulating the production of two pro-inflammatory cytokines, i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha), as well as the role of 5-HT(1A) and 5-HT(2) receptors in this process. The specific aims were to examine the effects of 5-HT, p-chlorophenylalanine (PCPA), a 5-HT depleting agent, flesinoxan, a 5-HT(1A) agonist, m-chlorophenylpiperazine (mCPP), a 5-HT(2B/2C) agonist, and ritanserin, a 5-HT(2A/2C) antagonist, on the production of the above cytokines. We found that: (1) 5-HT, 15 microg/ml, significantly decreased IL-6 and TNFalpha production; (2) pCPA, 5 microM, significantly suppressed the production of IL-6 and TNFalpha; and (3) mCPP, 2.7 microg/ml, significantly increased the production of IL-6 and TNFalpha. It is concluded that intracellular 5-HT is necessary for optimal synthesis of IL-6 and TNFalpha; 5-HT in physiological concentrations may increase IL-6 and TNFalpha production by stimulating 5-HT(2) receptors; and extracellular 5-HT concentrations above the baseline physiological levels may suppress the production of the above cytokines.     PMID: 15892984 [PubMed - indexed for MEDLINE] 1: Neuropsychopharmacology. 2000 Jul;23(1):89-98.Effects of serotonin and serotonergic agonists and antagonists on the production of interferon-gamma and interleukin-10.Kubera M, Kenis G, Bosmans E, Scharpe S, Maes M.Clinical Research Center for Mental Health, Anwerp, Belgium. Serotonin (5-HT) is a neurotransmitter and an immune modulator. In vitro, antidepressants with a serotonergic mode of action have, at concentrations within the therapeutical range, negative immunoregulatory effects, i.e., they increase the production rate of interleukin-10 (IL-10), a negative immunoregulatory cytokine. We have hypothesized that part of these effects may be explained by the serotonergic activities of antidepressants on immunocytes. This study was carried out to examine the effects of 5-HT, p-chlorophenylalanine (PCPA), a 5-HT depleting agent, flesinoxan (a 5-HT1A agonist), m-chlorophenylpiperazine (mCPP; a 5-HT2A/2C agonist), and ritanserin (a 5-HT2A/2C antagonist) on the production rate of interferon-gamma (IFNgamma), a proinflammatory cytokine, and IL-10 by whole blood stimulated with polyclonal activators. The IFNgamma/IL-10 production ratio was computed, since this ratio reflects the pro- versus anti-inflammatory capacity of cultured whole blood. We found that: 1) 5-HT, 150 ng/mL, 1.5 microg/mL, and 15 microg/mL significantly decreased the IFNgamma/IL-10 ratio; 2) PCPA (5 microM) significantly suppressed the production of IFNgamma and IL-10; 3) flesinoxan (15 ng/mL; 1.5 microg/mL) had no significant effects on the production of the above cytokines; and 4) mCPP (2.7 microg/mL) and ritanserin (5.0 microg/mL) suppressed the IFNgamma/IL-10 ratio. It is concluded that intracellular 5-HT may be necessary for an optimal synthesis of IFNgamma and IL-10, and that extracellular 5-HT concentrations at or above serum values may suppress the production of the proinflammatory cytokine IFNgamma. The negative immunoregulatory effects of antidepressive drugs are probably not related to their serotonergic activities.     PMID: 10869889 [PubMed - indexed for MEDLINE] 1: Int J Neuropsychopharmacol. 2002 Dec;5(4):401-12.    Effects of antidepressants on the production of cytokines.Kenis G, Maes M.Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, The Netherlands. g.kenis@...     There is now evidence that major depression is associated with an up-regulation of the inflammatory response system (IRS). One of the major factors in this IRS activation is the hyperproduction of pro-inflammatory cytokines. Recently, a number of studies examined whether there is a causative role of these inflammatory mediators in the aetiology of major depression. Studies with animal models and cytokine immune therapy in humans suggest that pro-inflammatory cytokines induce depressive symptomatology. Moreover, these depressive symptoms can be effectively reversed by antidepressant treatment. Thus, it may be suggested that antidepressants suppress pro-inflammatory cytokine production and/or action, resulting in improvement of depressive symptoms. The influence of antidepressants on cytokine production has been examined in culture systems in vitro, and in animal models of depression - in which cytokine production is induced by endotoxin administration. Results suggest that antidepressants of several classes decrease the production of pro-inflammatory cytokines such as interferon-gamma and tumour necrosis factor-alpha, and increase that of interleukin-10, an anti-inflammatory cytokine. Further, the effect of antidepressive treatment on cytokine secretion and on plasma levels of cytokines in depressed patients has been studied. Unfortunately, different approaches to examine cytokine production and different techniques to measure cytokines in plasma are used in these studies. Despite this, current data indicate a normalization of cytokine plasma levels and cytokine production after antidepressant treatment. It is clear, however, that more research is warranted and we strongly argue the need for higher standardization in the methodology used to examine the cytokine network in depressed patients.     PMID: 12466038 [PubMed - indexed for MEDLINE]  1: Circulation. 2000 Nov 14;102(20):2522-7.Serotonin increases interleukin-6 synthesis in human vascular smooth muscle cells.    Ito T, Ikeda U, Shimpo M, Yamamoto K, Shimada K.    Department of Cardiology, Jichi Medical School, Tochigi, Japan.     BACKGROUND: Interleukin-6 (IL-6) is a key molecule in chronic inflammation and has been implicated in the progression of atherosclerosis. Serotonin (5-hydroxytryptamine; 5-HT) causes vascular contraction and proliferation, but its role in atherogenesis has not been clarified. We investigated the effects of 5-HT on IL-6 synthesis in human vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: IL-6 levels in the culture medium of VSMCs were determined by ELISA. IL-6 mRNA accumulation was determined by use of a Quantikine mRNA colorimetric quantification kit. NF-kappaB activation was tested by gel retardation assay. 5-HT induced IL-6 production by VSMCs in a time- and dose-dependent manner, with increased IL-6 mRNA accumulation and nuclear factor-kappaB activation. The effect of 5-HT on IL-6 production was significantly inhibited by the 5-HT(2) receptor antagonist ketanserin and the selective 5-HT(2A) receptor antagonist sarpogrelate. Conversely, the 5-HT(2) receptor agonist alpha-methyl-5-HT increased IL-6 production. The protein kinase C (PKC) inhibitor calphostin C, but not the protein kinase A inhibitor KT5720, suppressed 5-HT-induced IL-6 production. The effect of 5-HT was also abolished in PKC-depleted VSMCs after pretreatment with phorbol 12-myristate 13-acetate for 24 hours. CONCLUSIONS: 5-HT acts on 5-HT(2A) receptors and increases IL-6 synthesis in human VSMCs at least partially through a PKC-dependent pathway. These results suggested that 5-HT may contribute to inflammatory activation of the vessels during atherogenesis.     PMID: 11076827 [PubMed - indexed for MEDLINE] 1: Toxicol Appl Pharmacol. 1996 Apr;137(2):157-62. Tricyclic antidepressants inhibit human natural killer cells. Xiao L, Eneroth P.Novum Clinical Research Center, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.     The commonly used antidepressants imipramine, amitriptyline, and nortriptyline were found to significantly inhibit human natural killer (NK) cell-mediated cytolysis in vitro and suppress the stimulation of NK cells by IFN-gamma. This is a previously unrecognized biologic property of these drugs with psychotropic activity. Tricyclic antidepressants did not decrease effector-target cell conjugation formation, nor did they induce target cell resistance to NK lysis, indicating that the drugs might interfere with the killing mechanism of the effector cells. Kinetic data reveal that the drug interference is related to an early postbinding event in the activation of NK cells. Results also showed that the inhibitory effect of tricyclic antidepressants on human NK cell activity occurred in parallel to an increase in intracellular cyclic GMP concentration. However, the attenuation in the cyclic GMP formation by methylene blue, a selective inhibitor of soluble guanylate cyclase, was not accompanied by a corresponding increase in NK cell cytolytic activity. It is suggested that the stimulation of cyclic GMP was not directly involved in the inhibitory effect of antidepressants on NK cells and perhaps was a secondary phenomenon. This immune cell modulatory property of tricyclic antidepressants seems to indirectly provide evidence for the concept that human brain neurons and NK cells might share regulatory system(s).     PMID: 8661340 [PubMed - indexed for MEDLINE]

[Guest guest]

try 5htp, it is a serotonin precursor, acts like prozac kindof. no side

effects . prescribed in europe and well tested there, amy

>I never really decided what I thought of this. Nicolson is the only

>one I've seen express the idea that they can obstruct abx therapy,

>and I dont know much about Nicolson.

>

>Personally the reason I finally hit the mirtazapine in April 2005

>was an immediate-term one... I didnt really know if mirtazapine

>would hinder abx therapy a bit, help therapy a bit, do nothing to

>therapy, but anyway I didnt really think it would be a huge factor,

>and I needed more appetite and motivation / motor drive (ALOT more)

>in order to be able to cook for myself, and thus be able to move

>back to Charlottesville for school.

>

> > It may be necessary to put a child with Lyme disease (or possible

> > infectious stew whatever) on an antidepressant. I thought I

> > remembered Dr. Nicholson writing that antidepressants suppress

>the

> > immune system. So I tried to read the following abstracts. I am

> > having trouble translating them into " good " or " bad. " I'm pretty

>sure

> > I got " bad " from the last article about tricyclics, but as for

>the

> > rest, I can't remember about TNF-greek-letter and interleukin-

>number

> > and what order things happen in. I just don't have a long-term

>memory

> > for these things, I guess! I would have to look them all up all

>over

> > again. So if anybody has any clues that will save me a few hours,

> > fire away!

> >

> > - Kate

>

>

>

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[Guest guest]

On May 2, 2006, at 6:19 PM, wrote:

> mirtazapine

This looks like an interesting drug. I just read that unlike SSRIs

and tricyclics, it improves REM sleep. The others tend to decrease

it. Also some other differences that sound good.

- Kate

[Guest guest]

There is some evidence that ADs have anti-inflammatory effects:

" Anti-Inflammatory effects of antidepressants through suppression of the

interferon-gamma/interleukin-10 production ratio. "

http://www.ncbi.nlm.nih.gov/pubmed/11270917

<http://www.ncbi.nlm.nih.gov/pubmed/11270917>

>

> I found this and it is a little bit old but I thought it was

> interesting. My guess is that it is damaging rather than beneficial.

> Anyone feel that they got sick more often when under AD's than

without?

>

> Marti

>

>

>

http://gumc.georgetown.edu/communications/facts/yearinreview200506.html

>

>

> Commonly Used Antidepressants May Also Affect Human Immune System

>

> Drugs that treat depression by manipulating the neurotransmitter

> serotonin in the brain may also affect the user's immune system in

> ways that are not yet understood, according to research done by Gerard

> Ahern, PhD, and a team of town scientists. The investigators

> found, for the first time, that serotonin is passed between key cells

> in the immune system, and that the chemical is specifically used to

> activate an immune response. They do not know yet, however, whether

> these SSRI (selective serotonin reuptake inhibitors) drugs-- including

> the brands Prozac, Zoloft, Paxil and others-- could have either a

> beneficial or a damaging effect on human immunity.

>

[Guest guest]

Hi - The study you quoted on the effect of ADs on IL-6, did not

actually test the effects of ADs on circulating IL-6, but instead was a

lab test done on stimulated blood samples. Instead, you might want to

read this study:

" IL-6 levels decrease with SSRI treatment in patients with major

depression. "

http://www.ncbi.nlm.nih.gov/pubmed/16158446

" RESULTS: The IL-6 levels showed no statistically significant

difference between the patients and the controls at baseline. However,

IL-6 levels after treatment with SSRIs were significantly lower

compared with the baseline IL-6 levels of both the patients and the

controls. "

- Mark

>

> Articles PMID 9367546 and 14996410 talk about stimulatory

> effects of serotonin type antidepressants on IL-6,

> and treatment resistant depression in relation to increased

> IL-6.

>

> http://www.pubmed.com

>

>

> Carol W.

> willis_protocols

> [see also my Links>Hormones & Neurotransmitters folder]

>