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Cholinergic drug and/or lipoic acid lowering fever? Why?

Discussion in 'Immunological' started by Ocean, Jun 4, 2012.

  1. Ocean

    Ocean Senior Member

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    Maye I'm making a cause effect assumption too soon as I've only tried this twice, but a cholinergic drug I've been prescribed for another medical issue seemed to bring down my fever. Granted, my temperature seems to vary quite a bit but so far two times I took it, my temp. lowered about 1 full degree or more. I noticed something similar when I took alpha lipoic acid as well.

    If these meds are really related to the lowering of my fever, can anyone guess why? I don't want to keep testing the connection because both the ALA and the med I took gave me side effects, so if I do try them again it won't be for a while. But I'm interested in the mechanism that may be behind this as maybe it will give me insight into my daily fever.
  2. rlc

    rlc Senior Member

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    Hi Ocean, what is the name of the drug?
  3. Ocean

    Ocean Senior Member

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    PM'd you, Ric.
  4. rlc

    rlc Senior Member

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    PM'd you back, Ocean
  5. Emootje

    Emootje Senior Member

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  6. adreno

    adreno 3% neanderthal

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    Cholinergics will also cause increased cortisol release, at least initially.
  7. Ocean

    Ocean Senior Member

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  8. Ocean

    Ocean Senior Member

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    That's interesting. It definitely gave me insomnia, I wonder if that is part of the reason.
  9. adreno

    adreno 3% neanderthal

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    Well, acetylcholine is an excitatory neurotransmitter in it's own right, known to impair sleep at higher levels. That's also why anticholinergics are sedating.
  10. Ocean

    Ocean Senior Member

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    Yeah, I was up all night when I took it at night. When I took it in the day it definitely got me up and active.
  11. Emootje

    Emootje Senior Member

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    Activation of the M1 muscarinic receptor in the brain also stimulates the cholinergic antiinflammatory pathway.
  12. lansbergen

    lansbergen Senior Member

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    http://www.ncbi.nlm.nih.gov/pubmed/11243565

    An independent non-neuronal cholinergic system in lymphocytes.

    Fujii T, Kawashima K.
    Source

    Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
    Abstract

    Acetylcholine (ACh) is a well characterized neurotransmitter occurring throughout the animal kingdom. In addition, both muscarinic and nicotinic ACh receptors have been identified on lymphocytes of various origin, and their stimulation by muscarinic or nicotinic agonists elicits a variety of functional and biochemical effects. It was thus initially postulated that the parasympathetic nervous system may play a role in modulating immune system function. However, ACh in the blood has now been localized to lymphocytes; indeed expression of choline acetyltransferase (ChAT), an ACh synthesizing enzyme, has been shown in human blood mononuclear leukocytes, human leukemic T-cell lines and rat lymphocytes. Stimulation of T-lymphocytes with phytohemagglutinin activates the lymphoid cholinergic system, as evidenced by increased synthesis and release of ACh and increased expression of mRNAs encoding ChAT and ACh receptors. The observation that M3 muscarinic receptor stimulation by ACh and other agonists increases the intracellular free Ca2+ concentration and upregulates c-fos gene expression strongly argues that ACh, synthesized and released from T-lymphocytes, acts as an autocrine and/or paracrine factor regulating immune function. These findings present a compelling picture in which immune function is, at least in part, under the control of an independent lymphoid cholinergic system.
  13. lansbergen

    lansbergen Senior Member

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    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518461/

    Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans

    I Wessler1,* and C J Kirkpatrick1
    Abstract

    Animal life is controlled by neurons and in this setting cholinergic neurons play an important role. Cholinergic neurons release ACh, which via nicotinic and muscarinic receptors (n- and mAChRs) mediate chemical neurotransmission, a highly integrative process. Thus, the organism responds to external and internal stimuli to maintain and optimize survival and mood. Blockade of cholinergic neurotransmission is followed by immediate death. However, cholinergic communication has been established from the beginning of life in primitive organisms such as bacteria, algae, protozoa, sponge and primitive plants and fungi, irrespective of neurons. Tubocurarine- and atropine-sensitive effects are observed in plants indicating functional significance. All components of the cholinergic system (ChAT, ACh, n- and mAChRs, high-affinity choline uptake, esterase) have been demonstrated in mammalian non-neuronal cells, including those of humans. Embryonic stem cells (mice), epithelial, endothelial and immune cells synthesize ACh, which via differently expressed patterns of n- and mAChRs modulates cell activities to respond to internal or external stimuli. This helps to maintain and optimize cell function, such as proliferation, differentiation, formation of a physical barrier, migration, and ion and water movements. Blockade of n- and mACHRs on non-innervated cells causes cellular dysfunction and/or cell death. Thus, cholinergic signalling in non-neuronal cells is comparable to cholinergic neurotransmission. Dysfunction of the non-neuronal cholinergic system is involved in the pathogenesis of diseases. Alterations have been detected in inflammatory processes and a pathobiologic role of non-neuronal ACh in different diseases is discussed. The present article reviews recent findings about the non-neuronal cholinergic system in humans.
  14. lansbergen

    lansbergen Senior Member

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    http://www.ncbi.nlm.nih.gov/pubmed/22270376

    The nicotinic acetylcholine receptor α7 in subcutaneous mature adipocytes: downregulation in human obesity and modulation by diet-induced weight loss.

    Cancello R, Zulian A, Maestrini S, Mencarelli M, Della Barba A, Invitti C, Liuzzi A, Di Blasio AM.
    Source

    Laboratory of Molecular Biology, IRCCS, Istituto Auxologico Italiano, Verbania, Italy.
    Abstract

    BACKGROUND:

    It is known that cholinergic anti-inflammatory reflex regulates inflammation in peripheral tissues. Nicotinic acetylcholine receptors (nAChRs) are mediators of this anti-inflammatory pathway and also non-neuronal cells express functional nAChrs. A role for α7-subtype acetylcholine cholinergic receptor (α7nAChR) in insulin sensitivity improvement has already been shown in rodents both in vivo and in vitro. However, no data are available on α7nAChR expression in human adipocytes.
    OBJECTIVE:

    To investigate the expression and protein content of α7nAChR in human subcutaneous adipose tissue (SAT) and in isolated mature adipocytes.
    DESIGN:

    A total of 39 SAT biopsy specimens obtained from obese and normal-weight subjects were used to assess α7nAChR messenger RNA levels and to stimulate α7nAChR with a specific agonist and antagonist in vitro. Additional SATs from eight non-diabetic obese subjects were also studied, before and after a 3-month lifestyle intervention.
    RESULTS:

    α7nAChR expression was significantly lower in the SAT of obese subjects compared with that of normal-weight subjects. In mature adipocytes isolated from morbidly obese subjects (body mass index>40 kg m(-2)), α7nAChR expression was 75% lower compared with adipocytes from normal-weight subjects. In adipocytes of obese subjects, α7nAChR was downregulated also at protein level. In eight non-diabetic obese subjects, a lifestyle intervention (3 months of diet and physical activity) induced a significant weight loss and an increase in α7nAChR SAT expression. In vitro stimulation of adipocytes with the specific α7nAChR agonist PNU282987 induced a significant anti-inflammatory effect. Furthermore, a similar downregulation of the inflammatory profile, associated with a significant increase in α7nAChR protein level, was observed after genistein stimulation.

    CONCLUSIONS:

    These results provide evidence that α7nAChR expression levels are significantly decreased in obese subjects, and that this receptor modulates inflammatory gene expression in human adipocytes. The upregulation of α7nAChR by genistein stimulation opens new insights for the management of low-grade inflammation linked to human obesity.International Journal of Obesity advance online publication, 24 January 2012; doi:10.1038/ijo.2011.275.
  15. lansbergen

    lansbergen Senior Member

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  16. alex3619

    alex3619 Senior Member

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    Cholinergic drugs will raise or lower cyclic AMP inside the cell, depending on the type of receptor. This will in turn have an opposite effect on ionized calcium. The cAMP/Ca++ form an axis, and a change in that balance could affect most other processes in an affected cell type. This is called cross-talk, where a signal from one receptor might affect a signal on another pathway. This might have something to do with an anti-inflammatory effect.

    Bye, Alex
  17. Ocean

    Ocean Senior Member

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    I think the ALA also has some sort of cholinergic effect it seems, when I looked it up there was some connection though I'm not sure exactly what.
  18. Emootje

    Emootje Senior Member

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    ALA is needed to convert pyruvate into acetyl CoA, an important component in the biogenic synthesis of acetylcholine.

    krebs.JPG
  19. Ocean

    Ocean Senior Member

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    What does it all mean?
  20. alex3619

    alex3619 Senior Member

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    It means that ALA is an essential component of the connection between glycolysis and the Krebs cycle - or to put it simply, ALA is needed to convert sugar into energy, but that energy substrate (Acetyl-CoA) can be diverted to making other things like acetylcholine. Its only one step however, and the real problem is likely to be in the mitochondria (where the Krebs cycle works). I personally suspect that ALA works more by boosting antioxidant capacity and so increasing Krebs cycle turnover, which means more Acetyl-CoA is available, though of course glycolytic input is still required to replenish the Acetyl-CoA. I am not sure that a slow down into the Krebs cycle is an issue however. I have never seen compelling data to show we have a reduced glycolytic capacity, even if my first model of CFS did propose such a thing. Also none of this takes into account the regulatory mechanisms in the steps for acetylcholine synthesis which I have never looked at closely. Bye, Alex

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