Treating cytokine up/down-regulation

[Jenny]

I wonder whether it's worth having a thread discussing what we know about treatments for over and under expressed cytokines, following Sunshine's very helpful post below:

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WPI & NCI

Type 1 IFN Pathyway Response to Viral Infection in Chronic Fatigue Syndrome

Mikovits,J. Hagen,K. Peterson,D. Stephens,R. Lombardi,V.

Whittemore Peterson Institute, Reno, NV, USA. Laboratory of Experimental Immunology, National Cancer Institute-Frederick, Frederick, MD, USA.


118 CFS patients
138 Controls

Cytokines/Chemokines:

CFS:

IL-8: 1045
MIP-1a: 763
MIP-1b: 1985
IL-6: 336
TNF-a: 148
IL-1b: 500
IP-10: 98
IFN-a: 35
IL-13: 28
IL-7 160

Controls:

IL-8: 13
MIP-1a: 91
MIP-1b: 164
IL-6: 29
TNF-a: 13
IL-1b: 56
IP-10: 32
IFN-a: 60
IL-13: 86
IL-7: 60


Guide to Chemokines/Cytokines:

IL-8: RNase L & CMV activated
MIP-1a: Elevated in neurodegenerative disease
MIP-1b: Elevated in neurodegenerative disease
IL-6: Stimulates chronic inflammation
TNF-a: Stimulates chronic inflammation
IL-1b: Stimulates chronic inflammation
IP-10: Interferon response protein
IFN-a:Stimulates macrophages and NK cells to elicit an anti viral response
IL-13: Inhibits inflammatory cytokine production
IL-7: Stimulates proliferation of B & T lymphocytes & NK cells



Summary and conclusions:

Cytokine and Chemokine profiling in combination with machine logic algorythms reveals an inflammatory signature consistent with an over-expression of herpes virus and is useful for diagnosis for CFS

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I think it's worth looking at studies on how depression is treated as this involves cytokine up and down regulation. There are there are quite a lot of studies on Pubmed on how anti-depressants affect cytokines. For example:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248234/

This found that sertraline lowered HDRS, and IL-12 and increased IL-4 and TgF-B1.

Others have found that anti-depressants inhibit TNF alpha and IL -1b.

I've been on sertraline for 7 weeks, starting at 12.5 mg and very slowly increasing to 50 mg a day. I've rarely felt at all depressed with this illness - in fact I'm pretty cheerful most of the time despite being bed-ridden for nearly a year with my current relapse, but I do get sudden episodes of a profoundly depressed feeling which last just a couple of minutes, particularly on waking, which are almost intolerable. They appear out of nowhere and disappear as suddenly. These have decreased over the last few weeks. Also I've hardly been able to eat anything for 6 months and lost a stone in weight (5 ft 6 in and only 8 stone) but three weeks ago my appetite returned to normal. I don't feel any better otherwise and am still bedridden, but now I've got this far with virtually no side effects I'm going to slowly increase to 100mg. (I don't actually have much optimism about this, but it's been an easy thing to try!)

Jenny

 

[Jenny]

Below is an article about experiences with sertraline.

Jenny

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Article for Interaction
From lying in bed all day listening to Radio 4, to riding a bike up steep hills or enjoying a night’s clubbing - how did we do it? This is another recovery story but with a difference.
My daughter, Sarah, and I had had ME for 8 and 6 years respectively when the recovery began. She was 16 when her illness started and I was 48. We had between us tried many treatments: diet [anti-candida and elimination], cold baths, massage, a healer [Seka Nikolic], geopathic stress analysis, osteopathy, homeopathy, acupuncture, herbs [Chinese and Western], vitamins and minerals, injections [magnesium, Vitamin C, gamma globulin, and interferon], galanthamine pills, anti-fungal pills, high dose antibiotics, anti-depressants [prothiaden and seroxat], relaxation techniques [Alexander and autogenic]; we had seen 3 consultants [2 NHS, 1 private]. All these helped other people, even cured them, but we seemed destined to be forever incurable - always in the two-thirds who were not improved in any research study. We were therefore seriously sceptical when we volunteered for one more research ‘experience’.
This is wherein lies the difference. I have returned to normal and Sarah is well on her way, simply by taking drugs. We were very suspicious of drugs and would have greatly preferred it, if the homespun remedies had done the trick, or, best of all, if our carefully controlled lifestyle had worked. They did not, but an SSRI has.
Dr. Ian James, Reader in Pharmacology at London’s Royal Free Hospital, set out to show that many ME patients could regain their health by taking Sertraline Hydrochloride [Lustral]. This drug is used with some graded exercise regimes, and to deal with depression. But Dr James excluded from his research anyone who was depressed, and told us to maintain our practice of doing less than we felt able to do. He had noticed that ME patients usually had ‘pupil wobble’ after a bright light had been flashed at their eyes. The pupil closed but then failed to open to the correct size; instead it wobbled away, letting in too much light & causing the hatred of brightness with which we were all too familiar. He used this to measure whether the drug was working before we could notice any changes. We had high tech pupillometry tests both before we took the Lustral and again after 6 weeks taking it. [We later learnt that an improvement in pupil wobble did indeed predict those who would later improve.]

Meanwhile we started to take the pills. This, however was easier said than done, because Dr James’ other discovery was how to prevent our bodies rejecting Lustral either immediately or 6 months later. He was the first doctor to point out to us that ME patients react badly to normal doses of drugs, although this made sense of various bad experiences we had both had during the illness. In order to deal with this problem we started on very small doses. The smallest Lustral pill is 50mg. We started on 12.5mg [Sarah took them every other day to be extra careful] and turned our kitchen table into something resembling a ‘drugs den’ as we crushed a pill & ‘cut’ it into 4 piles of white powder, which we then had to store for future days in tiny ‘wraps’.
We increased the dose very gradually every 4 days. But now came the hardest part-the 2 month’s wait to see if it would work for us. I became particularly worried that I might improve but not Sarah, a mother’s worst scenario.
One morning, about 7 weeks after taking the first pill, I woke from a heavy sleep and suddenly remembered that I always used to feel like that when I was normal! If you had asked me, I would have told you I had no sleeping problems with ME; but now I could make a comparison, I realised my sleep had been very light. The next few weeks were wonderful as, first, Sarah’s sleep changed, and then various symptoms, mostly in areas controlled by the brainstem such as cold heads, poor temperature controls throughout the body, disappeared. Interestingly enough we had been in Dr Costa’s research project at the Middlesex Hospital to measure blood flow in the brain. This showed that people with ME had too little blood in their brainstem, but had normal flow elsewhere in the brain. Could it be that the virus which caused ME in us had damaged the brainstem controls, and that the extra serotonin made available by the Lustral was improving the neurotransmission in that part of the brain? We became euphoric and made many overoptimistic plans but the euphoria was short-lived and not the result of the Lustral.
It has, in fact, taken 4 years for us to recover, and we have not yet reached total normality. Some symptoms were unbearably slow to depart: weird headaches, sore throats and lack of stamina were in this category, along with our tendency to catch every viral infection which is ‘going the rounds’.
We are now able to lead almost normal lives. I stay up 14.5 hours a day & sit in court as a JP, often taking the Chairman’s role in a busy central London court. I have at last resumed my social life, go out in the evenings, have returned to my kitchen and to large-scale cooking. I cycle round London at full speed, swim energetically and, above all, I am free of the tyranny of unrelenting self-control, with calculations of whether ‘if I do that, will I have to go to bed for 2 hours etc.? We both became expert at the ‘energy calculus’ but we are so pleased to have reintroduced spontaneity into our lives. Sarah’s social life is understandably more hectic. She hit the London social scene last year and has been making up for lost time. It is sometimes hard for me to believe the transformation in her appearance & her energy. She was once thin, white-faced & immobile, whereas now she speeds around rosy-cheeked & chatty; she has returned to her classical studies and is planning to complete her degree.
So why is this treatment not offered to everyone? Dr James found that 1% could not tolerate Lustral despite starting with low doses. But he also found that 80% of his sample improved. This is an amazingly high percentage. He excluded all whose illness had a nebulous onset but even so the results surprised. Sadly Dr James died before he could see our full recovery, and we will never know how many of the sample recovered completely because the Medical School have no interest in finishing the research. They point out that Dr James did not have a control group, and say that the whole piece of research would have to be repeated to ensure it was worthy of ‘peer review’ and publishable. They have nobody who wants to do this and, as ME is not a priority area for the hospital, they will take no notice of ‘patient need’. I wonder if any hospital makes ME a priority? Are we all to depend on the passing interest of hospital doctors?
When Dr James died the hospital washed its hands of us, sending us back to our GPs who can continue to prescribe us the drugs, but who know less about the treatment than we do. Luckily I kept notes of Dr James’ answers to my ‘what if’ questions and so we consulted these if we suffered a setback. But what about patients who were not so curious? Furthermore we now have a network of people who, having heard of our recovery from friends, consult us on the use of the drug. This is most unsatisfactory as we have no medical skills and cannot give such advice. Our present hope is that the Dept. of Health will soon reconsider research priorities as they affect ME.
We are very keen that as many people as possible have a chance to try this method of taking Lustral. It will not cure everyone but it will release some of you from the prison of ME out into the world again. Therefore we need someone urgently to redo this research – any suggestions?

Cynthia Floud
[This was written in 2000. I have now [2005] been off the pills for nearly 4 years [after 5 years on the pills]. This still amazes me. Sarah has just completed a degree at LSE and got a first. She stopped taking Lustral in mid 2004 after nearly 8 years. We are totally back to normal and can be as energetic as ever, without watching our step in any way.