Klimas: Plasma cytokines in women with chronic fatigue syndrome

[_Kim_]

November 12, 2009 Journal of Translational Medicine 2009, 7:96

Plasma cytokines in women with chronic fatigue syndrome by Mary Fletcher, Xiao Zeng, Zachary Barnes, Silvina Levis, Nancy Klimas

Results: The following cytokines were elevated in CFS compared to controls: LTalpha, IL-1alpha, IL-1beta, IL-4, IL-5, IL-6 and IL-12.

The following cytokines were decreased in CFS: IL-8, IL-13 and IL-15. The following cytokines were not different: TNFalpha, IFNgamma, IL-2,IL-10, IL-23 and IL-17.

Conclusions: Cytokine abnormalities are common in CFS. In this study, 10 of 16 cytokines examined showed good to fair promise as biomarkers.

However, the cytokine changes observed are likely to more indicative of immune activation and inflammation, rather than specific for CFS. As such, they are targets for 3 therapeutic strategies.

Newer techniques allow evaluation of large panels of cytokines in a cost effective fashion.

 

[Cort]

Thanks. the cytokine field is so confusing. None of the cytokines that the Whittemore Peterson Institute may be associating with XM RV, IL-8 and 6(?), I think, are elevated. (IL-8 is lowered!). Neither is IL-10 which has shown up elevated in several studies. Neither is TNF-a, a big important inflammatory cytokine, which a couple studies I believe suggest maybe elevated in chronic fatigue syndrome.

It's tough when the results are all over the map. Maybe this new way of looking at cytokines will have more consistent results over time. they are reportedly hard to measure

 

[kolowesi]

cytokine expression may change

I don't have any direct evidence, but I think I go through "cytokine storms" at various times.

I'm not sure what triggers them, but I know they make me feel really bad.

Once for a period of a year, I had a high ESR (sed rate). This is in spite of two clotting abnormalities, which usually cause the ESR to be lower than normal. At that time, my fibrinogen was very high, too! I wonder if I had been treating the fibrin, the ESR would have been even higher.

What I'm trying to say is that various genetics and infection responses can mask each other.

Dr. K might not have known all the co-morbid infections a given subject had, or all the pertinent genetics (such as clotting factor abnormalities or free radical related SNP's such as SOD2) which could muddy the results.

Next time I have what I think is a storm, I will try to get tested. BTW, even diet can affect cytokine expression. Hope more work gets done on this, as this is definitely connected to quality of life and cancer risk.

Kelly

 

[acer2000]

Dr. Peterson has measured my cytokines at various different times, probably 4 or 5 times in total. I can tell you that they have never been consistent. Sometiems they are totally normal, some times they are off the chart and different ones too. IL-8 does seem to be elevated in me, but to varying degrees and it always seems to go down if I take antibiotics. Curious for someone who supposedly has a viral infection. I think that the cytokine measurements are interesting from a research perspective, but I am not 100% sure they really know what they mean. Well, other than - if they are elevated you are sick - when they normalize it meants you are improving. Oh and if I think back to try to correlate my symptoms with the various cytokine measurements, my symptoms don't really seem to be all that different or dependent on what those tests show.

I once saw a paper on the web where the WPI was trying to associate various infections with different cytokine patterns, but I can't seem to find the link right now... Not sure if that research was ever replicated.

EDIT: Here is a link to the abstract - I still can't find the whole article - 36 Serum cytokine and chemokine profiles of individuals with myalgic encephalomyelitis (ME) reveal distinct pathogen associated signatures

As an aisde, I wonder about the accuracy of the assays in comparison to eachother (from both studies) - and also the effect of environmental differences - ie. people reacting to allergens differently in tahoe vs. florida, mold stuff... etc...

 

[Cort]

The generally weak and inconsistent cytokine measures in ME/CFS have been a problem for researchers trying to associate ME/CFS with an ongoing infection or inflammation. Specific cytokines are consistently upregulated in diseases like arthritis but they're not in ME/CFS. (See quote below). This is a real problem because people look at our cytokine responses and say that's not indicative of an ongoing infection.

Cytokines are consistently upregulated in people with an infection as they come down with ME/CFS but after that period its hard to find a really consistent finding. It could be that they're not looking in the right place but in other diseases they readily show up in the blood. They do not in CFS at least not consistently.

IL-1 and TNF-a have been implicated in pro-inflammatory mechanisms in many human diseases including inflammatory arthritis, inflammatory bowel disease, sepsis syndrome, and both acute and chronic inflammation of many organs (5,6). These cytokines are important in host defense against microorganisms that reside within cells, such as mycobacteria or listeria, as well as in other host defense responses and physiological processes.

 

[Cort]

I made a mistake; IL-6 was elevated in the study.

 

[Mark]

Cytokines are consistently upregulated in people with an infection as they come down with ME/CFS but after that period its hard to find a really consistent finding. It could be that they're not looking in the right place

Or it could be that they're not looking at the right time. If the cytokines spike relatively briefly whenever you encounter a trigger, you would have to test just at the time when a patient was having a reaction. Since the trigger and the reaction are both unknown, there's obviously no way to test that. Another version of the irony of only making it to see the doctor when you feel well enough perhaps?

 

[cold_taste_of_tears]

Cytokine assays are available at VIPdx in the USA and Red Labs in Belgium - Europe.

Exercise increases increases production of inflammatory cytokines in ME CFIDS
(Hence the worsening pain on exertion). It also lowers blood flow to the brain and creates
raised serum lactate, increased brain carbon dioxide. Hence the post exertional/vertigo inducing vascular headache
and cogntive decline - simply from walking around with this illness.

Graduated exercise programmes are pathalogically impossible to make the disease better - they create a relapse through immune activation.
Cytokins Assays show this.

Exercise in ME CFIDS would be like telling a Diabetic to gradually introduce Coca Cola.
Curiously the CDC doesn't understand this.

So Cytokine assays (especially if you can walk around, then get a big flare up afterwards of flu-like symptoms and muscle pain),
are are good test to have if you need evidence of inflammation and disabilty.

 

[Katie]

Cytokine assays are available at VIPdx in the USA and Red Labs in Belgium - Europe.

Exercise increases increases production of inflammatory cytokines in ME CFIDS
(Hence the worsening pain on exertion). It also lowers blood flow to the brain and creates
raised serum lactate, increased brain carbon dioxide. Hence the post exertional/vertigo inducing vascular headache
and cogntive decline - simply from walking around with this illness.

Graduated exercise programmes are pathalogically impossible to make the disease better - they create a relapse through immune activation.
Cytokins Assays show this.

Exercise in ME CFIDS would be like telling a Diabetic to gradually introduce Coca Cola.
Curiously the CDC doesn't understand this.

So Cytokine assays (especially if you can walk around, then get a big flare up afterwards of flu-like symptoms and muscle pain),
are are good test to have if you need evidence of inflammation and disabilty.

Thanks for that brilliant explanation. I've never had it explained to me before. I don't have anything constructive to add but that just made a lot of sense to me. Out of curiousity, do you know the abbreviation used for cytokine tests in the UK? I'm planning on having a look at my medical records when I'm feeling physically and mentally well enough, it would be interesting to see if they've tested my levels.

 

[George]

I've been trying to strike a balance

Cytokine assays are available at VIPdx in the USA and Red Labs in Belgium - Europe.

Exercise increases increases production of inflammatory cytokines in ME CFIDS
(Hence the worsening pain on exertion). It also lowers blood flow to the brain and creates
raised serum lactate, increased brain carbon dioxide. Hence the post exertional/vertigo inducing vascular headache
and cogntive decline - simply from walking around with this illness.

Graduated exercise programmes are pathalogically impossible to make the disease better - they create a relapse through immune activation.
Cytokins Assays show this.

Exercise in ME CFIDS would be like telling a Diabetic to gradually introduce Coca Cola.
Curiously the CDC doesn't understand this.

So Cytokine assays (especially if you can walk around, then get a big flare up afterwards of flu-like symptoms and muscle pain),
are are good test to have if you need evidence of inflammation and disabilty.

This certainly clears up that mystery. My doctor put me on the GET program told me to start with 1/4 mile a day and work up to 3. Needless to say I crashed and burned at about 1 mile a day. Was down for 6 months. He hasn't brought it up again.

But I have atrophy in the muscles now. How do you find a balance between just letting you self get worse and maintaining some kind of strength???

Umm if there is a thread on this just point me in the right direction. I don't mean to get off topic.

Thanks

 

[cfs since 1998]

But I have atrophy in the muscles now. How do you find a balance between just letting you self get worse and maintaining some kind of strength???

Umm if there is a thread on this just point me in the right direction. I don't mean to get off topic.

I don't know if there's a thread on this, but I will give a few comments on this topic. Jogging or even slow walking a mile is way too much for most of us. Besides, I think some kind of very mild weight training would be preferable to any kind of cardio work. What helps me is to do very, very short periods of exercise (less than 60 seconds) a few times per day. Don't try to increase it little by little ala GET. In fact, forget GET (this could be our new slogan...).

 

[Andrew]

I have some ideas about exercise. I realize this is off topic, but it seems important in this context.

I can move around my place a little. But at one point I was in bed all the time. A therapist showed me how to exercise lying down. Basically, I am just lifting my leg, bending my leg, tensing my buttocks, lifting my hips, bending my ankles, moving my leg out and back. Bending my arms, pushing my hands against each other, pulling arms apart while clasping hands. Putting palms up, and then palms down. Moving arms as if doing curls. When I learned these I was so weak I could only do 3 reps, and had to break this into two different times of the day. And later I learned that I could do these standing up.

Now that I'm doing significantly better, so I don't have to exercise lying down. I also got 6 pound weights for arm exercise. I just do basic stuff that comes to mind. I do three reps. I also lift my hands above my head (without weights) every day to keep shoulders flexible.

I can't say I have good discipline with all of this. But maybe someone else can do better.

Finally, when I was treated for cancer I was giving Juven to prevent muscle wasting. I later switched to Muscle Armour because it has the same core ingredients and tastes better. This stuff isn't cheap, but I take once a day instead of twice. My impression is that this helped me with muscle wasting problems. It also took away a weird felling I was getting in my muscles.

 

[JillBohr]

Cytokines in Autism

Very interesting in that I see many similarities in autism as well. My sources are all over the place but basically in autism

IL-4, IL-5, IL12 and IL-1 Beta are elevated

TNF alpha and IFN Gamma have no changes

The differences that I am seeing is that IL-6 is different according to some autism studies, some say elevated and others say no change. I was reading a Paul Ashwood paper (MIND Institute in CA) and he stated that IL-6 induces sleep.

http://www.jleukbio.org/cgi/content/full/80/1/1

I am also not sure about IL-10. According to one paper, this particular cytokine is not as active as it should be.

The finding that IL-10 levels were not elevated in individuals with autism, even when the levels of both Th1 and Th2 cytokines were elevated, suggests that the immune response dysfunction seen in autism may be a problem with regulating the cytokine system. Dr. Molloy hypothesizes that "children with autism may not be able to down-regulate their Th1 and Th2 systems" either because of a dysfunction in the production of IL-10 or because of a dysfunction with the activity of IL-10 itself.

http://www.autismspeaks.org/science/science_news/active_adaptive_immune_system.php

 

[Smulan]

Cytokines as biomarkers for CFS

I could not find any post on this interesting recent study.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779802/

"Cytokine abnormalities are common in CFS. In this study, 10 of 16 cytokines examined showed good to fair promise as biomarkers"

"The observations of abnormal cytokine patterns in CFS patients support the reports of retrovirus infections and reactivation of latent herpes virus infections. DeFreitas, et al found HTLV-II- like gag sequences by polymerase chain reaction and in situ hybridization as well as antibodies reactive with human T- lymphotropic virus (HTLV) in a majority of 30 CFS cases. Twenty healthy controls were negative for the three assays [11]. "

 

[fresh_eyes]

Good find, Smulan. I remember Nancy Klimas saying in an interview, something along the lines of, You don't have to believe in CFS like Santa Claus, CFS patients have all sorts of inflammation, you can measure it! Isn't that what cytokines represent?

 

[cfs since 1998]

Thanks for posting, I am surprised this hasn't received more attention considering it was published almost a month ago.

"The data from this study support a TH2 shift, pro-inflammatory cytokine up regulation and down regulation of important mediators of cytotoxic cell function."

Hasn't Dr. Cheney been saying there was a Th2 shift for like the past 10 years? Fresh_eyes, yes I believe Klimas was referring to inflammatory cytokines on that TV interview. She is the lead author of this paper.

 

[fresh_eyes]

OK, I'm realizing my crash course in retrovirology is not enough - now I need a course on how the immune system works!

I looked up some of the stuff CFS Since referred to:

General info about Th (T Helper) Cells:
http://en.wikipedia.org/wiki/T_helper_cell

Cheney on Th1 and Th2:
http://www.prohealth.com/library/showarticle.cfm?id=2911

 

[jewel]

Thanks, Smulan. Very interesting stuff here. I also will have to read up on the basics of the immune system. Thank, Fresh eyes, for the links! J.

 

[Smulan]

Its nice to see that this paper and dr Kerrs supporting something like a viral pathogen behind CFS

Take a look on IL-5. All PWCFS had higher levels then the controls. Perhaps IL-5 would be the most usefull for diagnostics?


.................... ME/CFS..................... Control...............................

Cytokin.......Med(low-high)............Med(low-high)..............average.

IL-5.. TH2...7.4 (6.3 - 10.0)...........3.8 (3.2 - 5.6)................+ 95

 

[consuegra]

Il-8

De Meirleir told me that IL-8 is often elevated in CFS/ME. Others have observed the same. This study indicates the opposite.

Chris

http://cfspatientadvocate.blogspot.com