Innate Immune Changes in the Peripheral Blood

[barbc56]

@Ecoclimber

I missed this link the first time I read your thread. If you don't mind, I will post the original URL.

http://scienceblogs.com/erv/2014/03/21/xmrv-the-rats-are-trying-to-climb-out-of-the-sewer/

Barb

 

[Valentijn]

Would corticosteroids have the same bad effects upon Borrelia infection as prednisone? I was diagnosed with exercise-induced asthma 4 years prior to getting acute ME onset (with Borrelia likely picked up 10-15 years earlier than that), and every corticosteroid I was prescribed just made me feel worse. Eventually a retired doctor filling in at my GP's clinic had me try Intal (Cromolyn sodium), which worked quite well.

According to my intermittently-legible medical records, I also had two short courses of antibiotics (azithromycin then levafloxacin) and a prednisone taper around the same time, when I was having sinus infections and worse breathing problems. Then I had a 3-week hemiplegic migraine which definitely started 3 days after I started some antibiotics - I think the levafloxacin.

 

[duncan]

Valentijn, I am going to assume you are directing your question toward me. If I am wrong, I apologize.

I am going to apologize again, because I am about qualify my answer. (the biggest qualifier is that I am no doctor, just a fellow patient) The general rule in many Lyme circles is to avoid immunosuppressive medications because they further compromise an already beleagured immune system struggling with Bb, and may worsen the infection. Keep in mind the patient potentially also may be dealing with co-infections which came courtesy of the tick. So the theory is your immune system is already working overtime, and the introduction of steroids - immunosuppressants - simply handicaps the body's ability to cope even further.

I believe Bussascano has written about what he reportedly called, "Steroid Disasters", i.e., Lyme patients that have been misdiagnosed and mistakenly been prescribed steroids, with the net effect being a dramatic worsening of symptoms. As to whether corticosteroids would have the same effect on Bb as prednisone, I am not sure, but as far as I can tell prednisone is a synthetic corticosteroid, and is an anti-inflammatory agent and is immunosuppressant, similar to other corticosteroids.

But every patient is an individual and every case peculiar, so sometimes steroids may be advisable even with bacterial conditions like Lyme, or other conditions that might seem to suggest steroids would be contraindicated. With a patient that has asthma, I'm not sure how a doctor would negotiate that complication should the patient develop Bb. My brother had asthma all his life, and he and I talked extensively about my Lyme - but not once did the two subjects ever come up in tandem during a conversation. I do believe even the most liberal of LLMD will sometimes treat Lyme patients with both abx and immunosupressent drugs because of the demands of the conditions presenting. Simply stated, there are exceptions to every general rule.

Edit to add: It may be interesting to note that my ME/CFS clinician wants to treat me with both abx for the Lyme, and immune modulators for the ME.

So far I have not acted on those recommendations.

 

[Gijs]

We looked at this study in another thread. The findings are interesting but unusual for autoimmune disease. It is unusual to see antibodies to more than one target of a particular type in a single patient - here several receptors. I would like to see the findings replicated by another group.

Thank you for your reply. Excuse me for guote professor Edward it is Edwards i see.

Is it possible when the sympathetic nervous system is in 'overdrive' (constantly) that the immunesystem get messed up? I think this is the case in ME.

 

[Gingergrrl]

@Valentijn, I have not read this thread and am only responding to something you said in your post without knowing the whole sequence.

In general, Levofloxacin (Levaquin) that you took can be neurotoxic and should never be combined with steroids which makes the potential reaction even worse. I wish that doctors understood this but they either are unaware or do not care. I just wanted to post to make sure that others are aware of this.

 

[Jonathan Edwards]

Thank you for your reply. Excuse me for guote professor Edward it is Edwards i see.

Is it possible when the sympathetic nervous system is in 'overdrive' (constantly) that the immunesystem get messed up? I think this is the case in ME.

That would be a novel suggestion but maybe possible. The immune system has sympathetic nerves feeding it and maybe the hypothalamus can send out signals to prime spleen and lymph nodes. It could be the other way around of course with the immune system priming or sensitising the sympathetic system. It looks to me fairly certain that the three big regulatory systems - brain, autonomic and immune are all involved in some way.

 

[Marco]

Thank you for your reply. Excuse me for guote professor Edward it is Edwards i see.

Is it possible when the sympathetic nervous system is in 'overdrive' (constantly) that the immunesystem get messed up? I think this is the case in ME.

It's not as simple as sympathetic high/parasympathetic low but in trying to tie the various findings together I came across the parasympathetic mediated 'cholinergic anti-inflammatory pathway' which could potentially link reduced parasympathetic activity/vagal tone to systemic low grade inflammation.

This is a Medical Hypotheses abstract but gives you the gist :

Physical activity, by enhancing parasympathetic tone and activating the cholinergic anti-inflammatory pathway, is a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

The CAP is an endogenous, physiological mechanism by which acetylcholine from the vagus nerve, interacts with the innate immune system to modulate and restrain the inflammatory cascade.

http://www.ncbi.nlm.nih.gov/pubmed/23395411

... and does have a solid scientific basis

The cholinergic anti-inflammatory pathway meets microRNA

The anti-inflammatory potential of the parasympathetic system has only been recently demonstrated1,2. The vagus nerve, the principal parasympathetic nerve connecting the nervous system with peripheral organs, can control inflammation in multiple settings of critical care

http://www.nature.com/cr/journal/v23/n11/full/cr2013128a.html


Not that exercise would appear to be a viable therapy for ME/CFS.


It's also worth noting that various central nervous system injuries can result in immune dysregulation :

Autonomic Nervous System Dysfunction & Inflammation: Autonomic-mediated immunomodulation and potential clinical relevance

The sympathetic nervous system provides the primary pathway for the neural regulation of immune function consequences of immunodeficiency triggered by CNS injury. Neurally mediated immunosuppression is adaptive and limits the extent of local or systemic inflammation.

The inflammatory-sensing and the inflammation-suppressing functions of the vagus may thus provide for an "inflammation reflex" that produces a rapid anti-inflammatory response.

Macrophages and monocytes respond to various stimuli by releasing proinflammatory cytokines, including tumor necrosis factor-alpha (TNFα), interleukin (IL)-1 beta (IL-1ß), IL-6, IL-12, and interferon gamma (IFNγ); these mediators are both effectors of inflammation and signal molecules to the nervous system"

http://www.natap.org/2013/HIV/052913_01.htm

 

[MeSci]

@Valentijn, I have not read this thread and am only responding to something you said in your post without knowing the whole sequence.

In general, Levofloxacin (Levaquin) that you took can be neurotoxic and should never be combined with steroids which makes the potential reaction even worse. I wish that doctors understood this but they either are unaware or do not care. I just wanted to post to make sure that others are aware of this.

I wonder why this isn't mentioned on this EU drugs site. All it says re steroid co-use is:

The risk of tendinitis and tendon rupture is increased in patients aged over 60 years, in patients receiving daily doses of 1000 mg and in patients using corticosteroids.

 

[Marco]

Rats!

This is an earlier but much better review of the cholinergic anti-inflammatory pathway :

The Cholinergic Anti-inflammatory Pathway: A Missing Link in Neuroimmunomodulation

This review outlines the mechanisms underlying the interaction between the nervous and immune systems of the host in response to an immune challenge. The main focus is the cholinergic anti-inflammatory pathway, which we recently described as a novel function of the efferent vagus nerve. This pathway plays a critical role in controlling the inflammatory response through interaction with peripheral α7 subunit–containing nicotinic acetylcholine receptors expressed on macrophages. We describe the modulation of systemic and local inflammation by the cholinergic anti-inflammatory pathway and its function as an interface between the brain and the immune system. The clinical implications of this novel mechanism also are discussed.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1430829/

 

[Jonathan Edwards]

Thanks to Marco for the detail. I should have said autonomic when I said sympathetic because it is clearly more complex.

 

[MeSci]

It's not as simple as sympathetic high/parasympathetic low but in trying to tie the various findings together I came across the parasympathetic mediated 'cholinergic anti-inflammatory pathway' which could potentially link reduced parasympathetic activity/vagal tone to systemic low grade inflammation.

This is a Medical Hypotheses abstract but gives you the gist :

Physical activity, by enhancing parasympathetic tone and activating the cholinergic anti-inflammatory pathway, is a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

http://www.ncbi.nlm.nih.gov/pubmed/23395411

... and does have a solid scientific basis

The cholinergic anti-inflammatory pathway meets microRNA

http://www.nature.com/cr/journal/v23/n11/full/cr2013128a.html
Not that exercise would appear to be a viable therapy for ME/CFS.

It's also worth noting that various central nervous system injuries can result in immune dysregulation :
Autonomic Nervous System Dysfunction & Inflammation: Autonomic-mediated immunomodulation and potential clinical relevance

http://www.natap.org/2013/HIV/052913_01.htm

Interesting. I don't have time to check out the links unfortunately, but will have to settle for a few comments on your comments and extracts.

People with ME seem to tend to benefit from sedating antihistamines, which are anticholinergic.

ME seems to share symptoms with organophosphate poisoning, which involves inhibition of cholinesterase and thus an increase in cholinergic activity.

But it is complicated by the fact that there are two (main?) types of cholinergic receptors, IIRC - muscarinic and nicotinic. Also IIRC agonism (activation) of the latter seems to be good for us, but antagonism (inhibition) of the former is also good.

I may have misremembered of course, but there are threads about these different receptors and therapeutic interventions involving them.

 

[lansbergen]

I use a positive α7 nAChR allosteric modulator.

 

[Marco]

Thanks to Marco for the detail. I should have said autonomic when I said sympathetic because it is clearly more complex.

You're welcome. Its an interesting concept which has been considered previously in respect to ME/CFS :

Neuroendocrine and Immune Contributors to Fatigue

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1430829/

 

[Marco]

Interesting. I don't have time to check out the links unfortunately, but will have to settle for a few comments on your comments and extracts.

People with ME seem to tend to benefit from sedating antihistamines, which are anticholinergic.

ME seems to share symptoms with organophosphate poisoning, which involves inhibition of cholinesterase and thus an increase in cholinergic activity.

But it is complicated by the fact that there are two (main?) types of cholinergic receptors, IIRC - muscarinic and nicotinic. Also IIRC activation of the latter seems to be good for us, but inhibition of the former is also good.

I may have misremembered of course, but there are threads about these different receptors and therapeutic interventions involving them.

Thanks. That's interesting.

It must be the nicotinic side for me. I was a very content ex-smoker for a number of years before ME/CFS hit.

 

[MeSci]

Rats!

This is an earlier but much better review of the cholinergic anti-inflammatory pathway :

The Cholinergic Anti-inflammatory Pathway: A Missing Link in Neuroimmunomodulation

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1430829/

Ah - my brain wasn't working too badly then - nicotinic! Saw your post after submitting mine.

 

[WillowJ]

If the severe reaction to a virus like EBV or enterovirus were a manifestation of an autoimmune process that was manifest as hyper-reactiveness to viruses then steroids might still help in the short term - as they tend to in people with EBV, even if later they may have prolonged fatigue. The patients DR Chia is worried about probably did get better initially, but then relapsed once the short term steroid course was stopped.

I find it quite hard to see how short courses of steroids would alter immune responsiveness in a way that would have long term implications.

Would it be logical to try a short course of steroids as a rescue drug for crashes/PEM? Sometimes we don't fully recover from these.

 

[justy]

Steroids for asthma seem to have played a part in my illness. I have since been diagnosed with chronic bacterial infections. Since that time I had to have a two course of prednisolone for severe asthma/lung symptoms and my health has once again worsened overall - although ALL the inflammatory symptoms in my body reduced so did my overall functioning which has not been regained. I am now left with no choice but to take high dose inhaled steroids.

For me steroids cause a good reduction in many symptoms (joint pain, ankle swelling, breathing, swollen lymph) but I alwsy feel much owrse M.E while taking them and usually crash. At one point I was left on too high a dose of inhaled steroids for 8 years (these are the 8 years I was in remission for so...?) and after some time I started to get more and more frequesnt infections and hormonal problems which cleared up gradually after I spent a year tapering it down. I sowre I would never take them again - but if you cant breathe - and I have some fibrosis in lung then what can you do?

KDM advised me to only take them as short a course as possible - sorry if not making a lot of sense - brain fog after catching up on this thread when I should be writing a 2,000 word essay about the hidden meanings in the fairy tale

 

[A.B.]

Hmm... I've also had asthma, following bronchitis. Several years before the first CFS symptoms appeared. Can inhaled cortisone affect the HPA axis or immune system?

 

[WillowJ]

KDM advised me to only take them as short a course as possible - sorry if not making a lot of sense - brain fog after catching up on this thread when I should be writing a 2,000 word essay about the hidden meanings in the fairy tale

I skipped over most of it.

Enjoy the essay and I hope you feel better.

Thanks for sharing your experience. I had prednisone only once, and I was worse after, but I had an allergic reaction to something else at the same time, so it was hard to tell what all the "worse after" came from (as the allergic reaction could have done that all by itself)

 

[Gijs]

You're welcome. Its an interesting concept which has been considered previously in respect to ME/CFS :

Neuroendocrine and Immune Contributors to Fatigue

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1430829/

Thank you for your reply Marco and professor Edwards. I think ME is a disease of the ANS everything else is secondary.