What is it about?
Inflammation has been defined for many years as the response to tissue injury and infection and has been recognized by the classic signs of rubor, tumor, calor and dolor - redness, swelling, warmth, and pain. Over the last few decades, however, dozens of conditions not accompanied by the classic signs of inflammation, with no evidence of tissue injury or infection, have been deemed inflammatory because increased concentrations of elements of the innate immune response or minor degrees of elevation of the acute phase protein serum C-reactive protein (CRP) have been found. We now know that metabolic stress and malfunction – deviations from the optimal homeostatic state - elicit molecules previously known to participate in inflammation, and which also act to restore optimal homeostasis. Accordingly, we propose that inflammation be redefined as the innate immune response to harmful stimuli such as pathogens, injury and metabolic stress.
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Why is it important?
This is important because the association between elevated CRP levels (or other participants in the inflammatory process) and a variety of conditions has generally been interpreted to indicate that inflammation plays a role in the pathogenesis of those conditions. (Such conclusions have often led to the suggestion that treatment with anti-inflammatory agents might be helpful.) However, that is not the only possible interpretation of such findings. When an association is found, the chicken and egg question always arises. In this case, the question is – is inflammation responsible for that condition, or does that condition elicit an inflammatory response? Our paper documents that the latter is indeed the case - a large variety of forms of metabolic stress can indeed elicit an inflammatory response. We can now think more clearly about the relationship between inflammation and metabolic stress.
Perspectives
I have been studying and publishing about CRP, from both clinical and basic science perspectives, for over 50 years. About two decades ago we became aware that minor degrees of CRP elevation predicted an increased likelihood of acute myocardial infarction in future years. The question arose: why should this be? The explanation was not clear. The presumption that CRP elevation reflected inflammation in coronary arteries did not make sense biologically, for a number of reasons. We then learned that that an astounding 30% of the American population displayed minor degrees of CRP elevation. Finally, we found that dozens of medical and unfavorable socioeconomic circumstances were associated with minor degrees of CRP elevation. Again, we had to ask – why? And now, finally, recent studies have explained these findings. The conclusions arrived at our paper put minor CRP elevation into appropriate perspective. Minor CRP elevation predicts acute myocardial infarction because it reflects the presence of metabolic stress (including the known risk factors for myocardial infarction - dyslipidemia, cigarette smoking, hypertension, diabetes, abdominal obesity, low levels of physical activity, and low levels of fruit and vegetable consumption). And minor CRP elevation is so prevalent in the population
Emeritus Professor of Medicine irving kushner
Case Western Reserve University
Read the Original
This page is a summary of: It’s time to redefine inflammation, The FASEB Journal, February 2017, Federation of American Societies For Experimental Biology (FASEB),
DOI: 10.1096/fj.201601326r.
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