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Strategies & Market Trends : Ask Vendit Off-Topic Questions -- Ignore unavailable to you. Want to Upgrade?

To: Jill who wrote (5594)	2/28/2005 7:35:37 PM
From: Walkingshadow	Read Replies (1) \| Respond to of 8752

<< I don't think inflammation gets turned on in the absence of infection. >> No Jill. Unquestionably, indisputably, inflammation can be turned on in the absence of infection. There is an avalanche of data to support that conclusion. The classic examples are arthritis and atherosclerosis (but there are many others). The former is definitely sterile. There is some question that the latter might be affected by infection, but generally the chronic inflammation that is the hallmark of atherosclerosis is a sterile inflammation. All autoimmune diseases involve sterile inflammation and their etiology has nothing to do with pathogens. And, by the way, statins---a spectacularly successful class of drugs to treat and prevent atherosclerosis-based diseases----works mostly because of anti-inflammatory effects. The clear benefit from statins has little to do with effects on serum cholesterol or lipoprotein profiles. The other major drug that has unquestioned benefit in preventing heart attacks and strokes is also an anti-inflammatory drug---aspirin. << I'm sure you know the research on antibiotics, even just a few weeks, lessening risk of 2nd heart attacks? >> Yes. There have been 22 randomized clinical trials that tried to prevent heart attacks etc. by giving antibiotics. These have involved over 25,000 patients. We conducted the largest one. None of these studies were able to show any preventive benefit at all from antibiotic therapy. (I am talking here about randomized, generally double-blind, placebo-controlled trials. Evidence suggesting involvement of pathogens was entirely derived from observational studies and anecdotal evidence, none of which had appropriate controls, and all of which was indirect, mostly correlational in nature.) Rheumatoid arthritis has nothing to do with infection. The clinical course of some chronic inflammatory diseases can be affected in one direction or another (not necessarily made worse) by pathogens (e.g., atherosclerosis, inflammatory bowel disease, etc.), but they are not caused by pathogens. With a few exceptions, there really is little evidence that most chronic inflammation has anything to do with ongoing infection. The immune system is extremely efficient at clearing pathogens, and when it is unable to completely clear them, it does the next best thing---- it most often neutralizes them in various ways, for example by walling them off (as in the case of tuberculous nodules, which basically cement the pathogen into a calcified nodule from which they cannot escape.) The question is not should inflammation be turned on or not. The problem is we don't know enough about immune regulation to allow fine tuning of things.... i.e., turning inflammation down or up as needed, and in localized fashion. This is a critically important goal for a number of reasons. Here's one: most people don't know this, but the vast majority of people who have cancer and die do not die of the cancer per se. They die of infection. True story. Now, cancer patients generally are not what you would call immunocompromised. Nevertheless, obviously there is something seriously, fatally wrong with the way they fight infection. I think it is important to find out exactly what that is. Similarly, it is important to find out why inflammation begins, is not attenuated or localized, and instead leads to chronic diseases in the absence of infection. These patients cannot be said to have hyperactive host defense mechanisms. The respond pretty normally to infectious challenge. Nevertheless, there's something very wrong deep within the web of the immune system. It is misleading and grossly oversimplified to say that the problem in virtually any disease characterized by chronic inflammation is overactive or underactive immune defenses. It is somewhat more accurate to say that in many of these diseases, the fine-tuning or turn-off signals have gone awry or gotten out of tune somehow, but clearly we need to know much much more about how these things work in the first place. T