The Cytokine Study was presented today (though some results were held back due to publishing). The study has been accepted by a journal but not published yet.
I have to say that this is the most well-designed and significant study of ME/CFS patients in the history of this disease. It has a large number of patients (200) matched by control patients. They accounted for variables that would make replication of the results easy to do.
We all know the disastrous mark left on ME/CFS research from the WPI XMRV study. This study more than makes up for that.
Dr. Montoya stated that ME/CFS presents the greatest medical and research challenge of our time and that understanding ME will help aid in the understanding of other diseases.
They studied 51 cytokines per patients in 200 patients comparing them to 400 healthy people. Patients and controls were matched according to age as well as other variables.
The current standard markers of inflammation (ESR, C-Reactive Protein) are increased in disease like RA and Lupus but not in ME. The typical inflammatory markers are normal in ME.
Dr. Montoya made the point that there are no inflammatory markers for ME because not enough of the inflammatory markers are measured.
Thus the cytokine study.
Cytokines are small proteins that the immune system uses (and are also produced by the immune system) to communicate between cells and pieces of the immune system. They can be used to communicate in small areas of the body or across major distances in the body.
Inflammation means fire so at its most basic understanding cytokines can be viewed as one way the body attempts to put out fires.
It's worth noting again that systemic inflammation shares similar symptoms with the flu.
The most immune concentrated areas are the lymph nodes, liver, spleen, bone marrow, thymus as well as other places. These organs produce cytokines that can be exported to other areas of the body.
ME is expressed by multiple disjointed symptoms in the body.
One reason why markers for ME are not picked up in the blood, the Montoya team postualtes, is that the inflammatory markers travel from the blood stream to the organ(s) affected. They shift from the blood to organs because there is inflammation in that particular organ or organs. Dr. Montoya believes the brain has major involvement.
Another interesting finding is that in mild ME cytokines decrease whereas in more moderate and severe disease they increase.
He believes this is the reason for such a discrepancy in findings in previous studies. Because there was no analysis according to disease severity the results of other studies evened out making the results appear deceptively normal. For example, one cytokine called Resistin is increased in moderately affected patients but decreased in the severely affected.
Also interesting is that the fire (inflammation) starts somewhere so the cytokines go there, and then other places.
When there are lower levels of cytokines in the blood it could mean they have shifted to the tissues that are inflamed.
IL-17 in particular is increased in severely affected patients. This is a clue to some sort of autoimmune process occurring.
Dr. Montoya believes there is a genetic factor that predisposes patients to ME.
He stated the the triggering factor could be infections, allergies, the environment--combined with the genetics results in ME.
Dr. Montoya, being an infectious disease specialist. postulates taht ME is the result of a hit and run mechanism. That some sort of insult causes a cascade of events and leaves the body in a damaged state.
He thinks its infection AND other factors,but not purely either, that affect the brain, heart, immune system, and digestive system.
He also believes there are subgroups.
He thinks viral onset patients might have a certain pattern of cytokine whereas other types of onset will show a different pattern.
Although a cure may never be discovered it will be possible to treat this disease thereby allowing us to function better, maybe even near normal and definitely good lives. Similar to lupus and RA patients.
Other inflammatory diseases are treated by anti-inflammatory agents. Dr. Montoya believes that some agents currently in use might be able to be used for treatment but there isn't enough info yet to determine which ones will be effective.
He cautions that the tricky part with ME is that one part of the immune system is overactive but another part is weak thereby leaving the door open to infection. Some of the anti-inflammatory treatments reduce the function of the immune system.
The whole secret will be how to use the anti-inflammatory drugs.
Regardless the stage has now been set for a host of things. Biomarkers for this disease, further research studies, new treatments, validation, and more funding for further studies.
Basically ME is a debilitating chronic systemic inflammatory disease.
Monday, March 17, 2014
I wrote in an earlier post that my symptoms increase during Winter particularly in rainy weather or when there is a low cloud layer also known as tule fog and/or inversion.
An inversion can lead to pollution such as smog/toxins/mold spores/chemicals being trapped close to the ground, with possible adverse effects on health.
When I wrote to my ME doctor (over a month ago) about my increase in symptoms, particularly depression, he wrote back that the weather is causing increased inflammation. Lisa Petrison, Ph.D and Erik Johnson wrote an interesting article called 'The Depression Response' (found in the blog section of their website). The article links the inflammatory response to toxins and has an interesting take on depression.The website itself (Paradigm Change) is a fascinating read.
The word 'inflammation' comes from the latin word 'inflammare' which means 'to set on fire'. Everyone who has suffered a skin infection knows about the redness that develops as a result of inflammation. What I hadn't realized until recently is that the redness isn't a result of the infection per se but the body's response to the infection.
The inflammatory response can occur as a result of infections, trauma, and toxins. The symptoms of inflammation are similar to those of an infection (flu like symptoms).
The immune system protects the body from harmful substances by recognizing and responding to things called antigens. Antigens are substances found on the surfaces of cells, viruses, bacteria, and fungi. They are also nonliving substances such as toxins, chemicals, and drugs.
An efficient immune response protects against many diseases and disorders. An inefficient immune response allows diseases to develop. Too much, too little, or the wrong immune response causes immune system disorders. An overactive immune response can lead to the development of "autoimmune diseases," in which antibodies form against the body's own tissues.
Complications from altered immune responses include:
- Allergy or hypersensitivity
- Autoimmune disorders
- Immunodeficiency disorders
As its name suggests, the innate immune system consists of cells and proteins that are always present and ready to mobilize and fight microbes at the site of infection. The main components of the innate immune system are 1) physical epithelial barriers, 2) phagocytic leukocytes, 3) dendritic cells, 4) a special type of lymphocyte called a natural killer (NK) cell, and 5) circulating plasma proteins.
Cells of the innate immune system include phagocytic cells (monocyte/macrophages and PMNs), NK cells, basophils, mast cells, eosinophiles and platelets.
The innate immune system lacks discrimination among antigens and can be enhanced after exposure to antigen through the effects of cytokines.
The adaptive immune system, on the other hand, is called into action against pathogens that are able to evade or overcome innate immune defenses. Components of the adaptive immune system are normally silent; however, when activated, these components “adapt” to the presence of infectious agents by activating, proliferating, and creating potent mechanisms for neutralizing or eliminating the microbes. There are two types of adaptive immune responses: humoral immunity, mediated by antibodies produced by B lymphocytes, and cell-mediated immunity, mediated by T lymphocytes.
ME patients have faulty immune systems. Part of the immune system is overactive as if it is constantly battling some sort of insult while another part is weak which allows infections to reactivate.
I think it's interesting that toxins and chemicals can cause inflammation. I hadn't realized that before. I also find it interesting that constant inflammation can affect the immune system creating a vicious cycle. Inflammation lowers immunity and lowered immunity allows toxins/chemicals/infections to create more inflammation and on and on.
It seems an ideal treatment would be to dampen inflammation, reduce the toxic load on the body, moderate the immune system, fight infections, and detoxification.
For me I had to leave the moldy environment I was living in. I have to stay vigilant of staying away from other moldy environments (certain molds) or if I notice certain symptoms that indicate I'm in a toxic environment (feeling faint, sensory storms, unexplained swollen lymph nodes, muscle weakness) I need to leave immediately and take other actions.
I'm also on an immune modulator, antivirals, a low dose antibiotic, support for adrenals/thyroid, and various supplements.
Treatments did not work at all while I was living in a toxic moldy environment. I have a genetic susceptibility to mold/toxins/infections. Similar to alcoholism once my body reached a certain toxic threshold there was no going back and I lapsed into ME. My body cannot effectively eliminate toxins (especially mold) or infections on its own.
I've had great improvement by doing the above. I still can't work but I have a social life and am able to leave the house on most days whereas before I my functioning range was bedbound to 90% housebound. Regardless I needed to be laying down 20 hours per day.
Now I can be upright a majority of the day, and as stated above, can leave the house most days. My PEM has lessened considerable as has my POTS. My digestive system has improved.
I think if I moved to a drier climate where I could be outside for much of the time I would do even better and possibly even be able to stop some of the medications I'm on.
Posted by me/cfs warrior at 6:41 PM