A few days ago I responded to a post in which members were questioning if statins had caused PMR. I have received messages asking for more information about my comments. In response to these questions I have written the following which I hope will be of interest and help. I am a retired clinical Pharmacist of some 35 years experience and have referenced my research should any of you wish to read in more depth:
Interleukin 6 and its role in inflammatory diseases including PMR and GCA
The immune system is essential for our survival by recognising and eliminating infectious pathogens which include bacteria and viruses. Sometimes however this highly sophisticated and complex process fails to recognise us and the process escalates and begins to attack our own tissues. Genetic and environmental factors can play a part and sometimes this heightened immune response doesn’t switch off fully and continues to chug along in the back ground with little obvious effect other than the odd ache, pain, skin rash or tiredness. As the inflammation in the body builds, more non-specific symptoms may show which prompts us to seek medical advice or perhaps we get an infection which causes another immediate immune response which triggers a massive production of cytokine.
The immune response is a complex defence mechanism in which many different substances are produced by white blood cells, T-cells and damaged tissue cells. The resulting inflammation is either acute, having a short and limited response time or it is chronic, which is often a persistent phenomenon that can also lead to tissue damage. In such cases the result is an auto-immune disease of which there are many and include Rheumatoid arthritis, Graves disease, Systemic Lupus Erythematosus, PMR, GCA, Psoriasis, Multiple sclerosis, Type 1 diabetes. What we end up with will largely depend on our genetic make-up and the susceptibility of our organs and tissues. Many different chemicals are produced during the inflammatory response and one of these is Interleukin 6, a cytokine. IL-6 is unusual because initially it switches on the acute phase response, it’s a good guy. Unfortunately, in chronic inflammatory situations it becomes pro-inflammatory, a bad guy. In auto-immune disease it not only maintains the inflammatory process but also modifies the immune response and accelerates the disease process.
In addition to this, if IL-6 is generated in the bone marrow it affects osteoclasts. These cells are responsible for breaking down bone and osteoporosis can result. In the bone marrow it promotes a process which leads to over production of platelets. It also affects the regulation of serum iron and zinc levels. In the liver, IL-6 causes CRP (C-reactive protein) to be produced.
So what does this mean in practice? We have blood tests which help our doctors understand what is going on. A raised platelet count, reduced serum iron, reduced serum zinc, raised CRP all point towards elevation of Interleukin -6. Almost all chronic inflammatory disease in which CRP is also elevated are thought to be caused by raised IL-6 levels. Doctors will also order an ESR (erythrocyte sedimentation rate) or sed rate. An ESR is not a stand-alone diagnostic tool but together with other blood tests helps build a picture to assist in diagnosis and as an aid to evaluate effectiveness of treatment. The value of the ESR result gives a measure of the degree of inflammatory activity but does not give any clue as to what the cause is. If ESR and CRP results are compared following treatment it is not uncommon to see a lag. ESR values do not change as rapidly as CRP due to physiological reasons. CRP values tend to fall more quickly and are a more reliable indicator that treatment is working. ESR is usually raised in PMR, GCA and RA. CRP is usually raised too and as already stated can be because of the presence of IL-6 but an infection will also raise CRP levels.
Because we are all genetically different (except identical twins!) there will always be differences between us which is why our symptoms vary, our response to treatment varies and even our ESR/CRP results vary. PMR and GCA are auto-immune diseases which present us and our doctors with huge challenges because we are all so different. The only common factor is that they are caused by an over-production of Interleukin 6. The “cure” is to stop our bodies over-producing it and the treatment is to block its effect on our tissues. Sadly I don’t have the answer to that.
There is a very complex theory explaining why corticosteroids (prednisone and prednisolone and their derivatives) are thought to work in IL-6 mediated diseases. The newer biological agents like Tocilizumab are monoclonal antibodies of the Immunoglobulin G1 class and it works specifically by preventing the IL-6 from binding to the tissues.
The novel interleukin-1 cytokine family members in inflammatory diseases.
Hahn M1, Frey S, Hueber AJ.
Interleukin 6 in autoimmune and inflammatory diseases: a personal memoir
Interleukin-6 and chronic inflammation
Cem Gabay 1
IL-6 in Inflammation, Immunity, and Disease
Toshio Tanaka,1,2 Masashi Narazaki,3 and Tadamitsu Kishimoto4