(Editors note: This is a report by Ella's mother Michele, a very active contributor to www.cpnhelp.org and user of the protocol herself. They began the CAP in the crisis of Ella's rapid deterioration and the change since then is quite remarkable though the story is far from over. It illustrates well the judicious use of steroids to manage inflammatory symptoms while slowly ramping up on the CAP. Most of us have followed Ella's progress with enthusiasm and bated breath. She's kind of become a mascot for many of us more "mature" types, symbolic of the restoration of vigorous life were this treatment started when we were younger! We will add to this update as her treatment progresses.)
Body response, often an immune/cytokine response, to infection or other foriegn agent.
I am very excited to present the following article that summarizes Dr. Stratton's recent observations on Chlamydia pneumoniae infection. Putting it together has contributed greatly to my own understanding of Cpn as well as to my appreciation of Dr. Stratton's generosity with his time, and his great depth of knowledge of this area. Thanks to him for his contribution. Jim K Recent observations by Dr Recent observations by Dr. Charles Stratton on Chlamydia Pneumoniae (Cpn) Infection
I don't believe we have this linked to our Research Pages (Marie?). This is a brilliant dissertation from the Finnish group, some of the world's experts on Cpn as some of the faculty in Helsinki were part of the original group who discovered the very existence of Cpn.This dissertation demonstrates a number of important findings:
- Repeated infection with Cpn "...induced persistent chlamydial DNA and inflammation in lung tissue and development of mouse Hsp60 autoantibodies."
- Repeated infection with Cpn "...significantly increased subendothelial lipid accumulation in the aortic sinus area."
- That "A flavonoid, luteolin, was shown to effectively decrease the chlamydial load and inflammatory reactions in lung tissue." Note: luteolin is not the same as lutein.
- Conventional antimicrobial treatments are not effectively to eradicate persistent infection.
Go to the link and you can download the whole thing in pdf form. Experimental Chlamydia pneumoniae infection model: effects of repeated inoculations and treatment
Lääketieteellinen tiedekunta, Oulun yliopisto
Russell Farris and Per Marin MD PhDThe potbelly syndrome: how common germs cause obesity, diabetes and heart disease.Basic Health Publications Inc, Laguna Beach, CAPp 246 ~ Paperback $17.95 (US) $23.95 (Canada)Reviewed by David Wheldon MB FRCPathThis book explains how common, non-resolving intracellular infections can, over long periods of time, subvert the body's defences by causing chronic elevation of cortisol while provoking chronic activation of pro-inflammatory cytokines; this has serious repercussions, including type II diabetes, atheroma and heart disease. Much of what we put down to ageing is caused by chronic infection.
I have culled from Mitchell & Stratton patent #6,884,784 an exhaustive list of diseases where Cpn has been implicated as a possible cause or co-factor (reference: Mitchell & Stratton patent #6,884,784):
Diseases where an association has been discovered between chronic Chlamydia infection of body fluids and/or tissues with several disease syndromes of previously unknown etiology in humans which respond to unique antichlamydial regimens include:
Editorial comment: Strong findings from their research. If you have any of these it suggests to me that at least an empirical course of the combination antibiotic therapy is strongly indicated, with or without serology. Multiple Sclerosis (MS) Rheumatoid Arthritis (RA) Inflammatory Bowel Disease (IBD) Interstitial Cystitis (IC) Fibromyalgia (FM) Autonomic nervous dysfunction (AND neural-mediated hypotension); Pyoderma Gangrenosum (PG) Chronic Fatigue (CF) and Chronic Fatigue Syndrome (CFS).
Infect Immun. 2004 Nov;72(11):6615-21. Related Articles, Links
Differences in cell activation by Chlamydophila pneumoniae and Chlamydia trachomatis infection in human endothelial cells.
Krull M, Kramp J, Petrov T, Klucken AC, Hocke AC, Walter C, Schmeck B, Seybold J, Maass M, Ludwig S, Kuipers JG, Suttorp N, Hippenstiel S.
Department of Internal Medicine/Infectious Diseases, Charite, University Medicine Berlin, Augustenburger Platz 1, 13353, Germany. firstname.lastname@example.org
Seroepidemiological studies and demonstration of viable bacteria in atherosclerotic plaques have linked Chlamydophila pneumoniae infection to the development of chronic vascular lesions and coronary heart disease. In this study, we characterized C. pneumoniae-mediated effects on human endothelial cells and demonstrated enhanced phosphorylation and activation of the endothelial mitogen-activated protein kinase (MAPK) family members extracellular receptor kinase (ERK1/2), p38-MAPK, and c-Jun-NH2 kinase (JNK). Subsequent interleukin-8 (IL-8) expression was dependent on p38-MAPK and ERK1/2 activation as demonstrated by preincubation of endothelial cells with specific inhibitors for the p38-MAPK (SB202190) or ERK (U0126) pathway. Inhibition of either MAPK had almost no effect on intercellular cell adhesion molecule 1 (ICAM-1) expression. While Chlamydia trachomatis was also able to infect endothelial cells, it did not induce the expression of endothelial IL-8 or ICAM-1. These effects were specific for a direct stimulation with viable C. pneumoniae and independent of paracrine release of endothelial cell-derived mediators like platelet-activating factor, NO, prostaglandins, or leukotrienes. Thus, C. pneumoniae triggers an early signal transduction cascade in target cells that could lead to endothelial cell activation, inflammation, and thrombosis, which in turn may result in or promote atherosclerosis.
Am J Respir Cell Mol Biol. 2005 Dec 9; [Epub ahead of print]
Mechanisms of Chlamydophila pneumoniae Mediated GM-CSF Release in Human Bronchial Epithelial Cells.
Krull M, Bockstaller P, Wuppermann FN, Klucken AC, Muhling J, Schmeck B, Seybold J, Walter C, Maass M, Rosseau S, Hegemann JH, Suttorp N, Hippenstiel S.
Department of Internal Medicine/Infectious Diseases, Charite, Universitatsmedizin, Berlin, Germany.
Chlamydophila pneumoniae is an important respiratory pathogen. In this study we characterized C. pneumoniae strain TW183-mediated activation of human small airway epithelial cells (SAEC) and the bronchial epithelial cell line BEAS-2B and demonstrated time-dependent secretion of granulocyte macrophage colony-stimulating factor (GM-CSF) upon stimulation. TW183 activated p38 mitogen activated protein kinase (MAPK) in epithelial cells. Kinase inhibition by SB202190 blocked chlamydia mediated GM-CSF release on mRNA- and protein-level. In addition, the chemical inhibitor as well as dominant negative mutants of p38 MAPK isoforms p38alpha, beta2, and gamma inhibited C. pneumoniae-related NF-kappaB activation. In contrast, blocking of MAPK ERK, c-Jun kinase/JNK or PI-3 Kinase showed no effect on Chlamydia related epithelial cell GM-CSF release. UV-inactivated pathogens as compared to viable bacteria induced a smaller GM-CSF -release suggesting that viable Chlamydia were only partly required for a full effect. Presence of an anti-chlamydial outer membrane protein-A (Omp-A) antibody reduced and addition of recombinant heat-shock protein 60 from C. pneumoniae (cHsp60, GroEL-1) enhanced GM-CSF -release suggesting a role of these proteins in epithelial cell activation. Our data demonstrate that C. pneumoniae triggers an early proinflammatory signaling cascade involving p38 MAPK dependent NF-kappaB activation resulting in subsequent GM-CSF release. C. pneumoniae-induced epithelial cytokine liberation may contribute significantly to inflammatory airway diseases like chronic obstructive pulmonary disease (COPD) or bronchial asthma.
Nitric oxide has long been suspected as the possible damaging factor in multiple sclerosis. The logic goes like this: The body for some unknown reason starts attacking the brain as if it were a foreign protein (like a bacteria). The microglia (the cells in the brain which are responsible for immune responses that might be needed inside the blood brain barrier-the regular white blood cells are kept out by the BBB)produce large amounts of nitric oxide (NO) which damage the nearby nerves and support cells. If only we could get rid of the NO then we could control MS. An example of this kind of research can be found HERE. Also another one HERE. It is clear that the researchers consider the production of NO an abherrent and undesirable response and a contributor to autoimmunity. You might note that they also are very clearly believing the autoimmune model. Many physicians and researchers forget that this is just a model, not a proven fact.
David Wheldon and Dr A were asked about the reason that steroids and immunosuppressants do not cause CPN to go out of control in the case of MS. If people with MS actually have CPn, why are steroids or things like tysabri apparently helpful? Why do they not make people worse? answer follows:
DR A's response (the MD who is close to the VU work who is expert)
As far as steroids are concerned, the cellular immune system isnâ€™t very effective against C. pneumoniae infections (The C. pneumoniae can infect every cell in the cellular immune system.). Therefore, interfering with the cellular immune system ( by giving something like steroids or suppression of the immune system ed.) would be predicted to have little to do with making the disease worse â€“ and might make the symptoms better if the symptoms were related to inflammation.