- Immune response
The ability of our bodies to distinguish self from non-self is essential to our survival but under certain circumstances inter alia rheumatoid arthritis, this defense aparatus can be turned on the bodies normal tissues. Antigens
Inflammation is a term which has ancient origins, which originally describe the characteristic clinical manifestations of calor, rubror, dolor, tumor and functio laesa. Inflammation is a stereotypical set of cellular responses that give rise to local and systemic physiologic changes, classically in response to infection but also in response to injury and irritation. All are circumstances which warrant a change in behavior and a shift in priorities in a timely manner to confront a threat which may not be entirely evident absent this response. Indeed when the immune system is compromised this early warning system fails to promote the necessary cascade of events that give rise to a robust response to the offending agent, actual or potentially injurious circumstance. Inflammation plays a propitious role in all normal healing responses and thus it is not the enemy but rather the messenger albeit the bearer of bad news which is ignored at our peril.
The ubiquitous nature of this cellular response may lead us to conclude that it is always the source of pain where it occurs without aparent cause and thus we tend to assume this mechanism is at work for any malady involving pain even if dolor and functio laesa i are the only manifestations, tendinopathies may be an example of this tendency.
- Monocytes and Macrophages
- Mast Cells
- Aspirin and NSAIDS
Message in a bottle.
We inject a glucocorticoid without giving it much thought. It is our one blunt instrument for influencing the immune system which is slowly revealing its secrets through the laborious efforts of clinical investigators and basic scientists. Meanwhile, if it hurts and it is not getting better and if a surgery does not seem warranted then odds are we are likely to see if bathing the problem area in glucocorticoid will help out. The practice came into being on the premise that many painful conditions were caused by inflammation and thus might respond to an anti-inflammatory. Many conditions previously felt to involve inflammation are later found to be some other process for which we stuggle even to find a suitable name.Yet we are left without an explanation for what seems at least to be a substantial degree of effectiveness to the injection of a glucocorticoid. Glucocorticoid effects a variety of cell types unrelated to inflammation. Its influence in these cases may be via some other mechanism, involving the gene expression of the targeted cells. The influence of the glucocorticoid is not necessarily helpful or neutral, it may also be harmful beyond simply side effects like fat atrophy and skin depigmentation. Cellular apoptosis, tendon rupture or a more insidious state of arrested remodeling, halting a productive healing process in the interest of alleviating acute symptoms and in the process creating a cycle of chronic or recurrent difficulties if not inciting the rupture of a tendon or the deterioration of joint cartilage.
Approaching 60 years since the discovery of a glucocorticoid receptor and the first clinical use of systemic steroids for the treatment of rheumatoid arthritis and we as yet to not have complete knowledge of the molecular mechanism of action of glucocorticoids. A dermatologist may use a short course of systemic steroids 30 times a week in his office population, a rheumatologist may have innumerable patients on low dose prednisone for years. Chronic COPD for the pulmonologists.
Glucocorticoids act on most cells, the molecule binds to a carrier molecule within the cell and is transported to the nucleus where it influences, usually down regulates DNA transcription.
Cyclooxygenase COX is the major enzymatic target of most of the anti-inflammatory medications we use as clinicians. This enzyme controls the arachidonic acid metabolism and is present in three isoforms; types 1 and 2 are periferal and type 3 central.
- New Horizons