Immune Selective Anti-Inflammatory Derivatives (ImSAIDS) are a new class of immune-therapeutic agents under active research by several laboratories and which are already produced for veterinary use by the IMULAN corporation right here in Arizona. Currently, the most interest is in the tripeptide phenylalanine-glutamate-glycine in its D-isomeric form (feG.) feG has been shown to modulate states of activation and migration capability on neutrophils circulating within an experimental system (Mathison, et al. 2003.) The specific mechanism of action appears to be by disruption of leukocyte migration into inflamed tissues, resulting in a lower rate of free radical production and oxidative damage therein.
The primary therapeutic advantage of agents like feG over traditional steroids and NSAIDS is that ImSAIDS do not cause a systemic reduction in immune activity; instead, they tend to down-regulate acute immune responses (Mathison, et al. 2003.) Two clinically-pertinent examples of destructive acute immune responses have been studied and found to be potential targets for feG therapy, anaphylaxis and spinal cord inflammation after injury. When rats were challenged with a pro-anaphylatic antigen, Turesin, et al, showed that feG was effective at preventing a destructive, systemic inflammatory response (2002.) Bao, et al, studied a rat model of acute physical spinal damage and showed that feG was capable of preventing neutrophil activity in damages tissue by as much as 48% resulting in a marked reduction in secondary, inflammation-related damage to spinal cord tissue (2006.) A secondary advantage observed in all known studies on feG to date is that therapy with the agent appears to present no potential toxicity.
IMSAIDS are currently being investigated for the treatment of sepsis, anaphylaxis, acute trauma, pancreatitis, cystitis, allergies and asthma. In theory, they could be applied to any situation where an inappropriate or exaggerated immune response is present, with the added benefit of not completely attenuating the immune system. They will, no doubt, be a welcome addition to the arsenal of rheumatologists and other clinicians when they are studied in humans to a greater extent.
A comprehensive review article can be found at: http://www.journal-inflammation.com/content/7/1/49
Mathison -> PubMed 12659660: http://www.ncbi.nlm.nih.gov/pubmed/12659660
Turesin -> PubMed 12199907: http://www.ncbi.nlm.nih.gov/pubmed/12199907
Bao -> PubMed 16581192: http://www.ncbi.nlm.nih.gov/pubmed/16581192
This is a very interesting topic. ImSAIDs or Immune-Selective Anti-Inflammatory Derivatives represent those peptides being commercially developed for their biological properties such as the anti-inflammatory properties of the peptide feG. These peptides seem to work by decreasing the damaging effects of inflammation in multiple ways. They have been shown to not only decrease the number of certain circulating granulocytes but also affect the cellular adhesion molecules involved in leukocyte extravasation and affect intracellular neutrophil ROS. These decrease over-activation of leukocytes, systemically, without causing obvious immune-suppression or toxicity. By influencing leukocytes in this broad manner the activity of ImSAIDs show promise for use beyond the scope of current NSAID and steroid therapies.
ReplyDelete1. Mathison RD, Christie E, Davison JS. The tripeptide feG inhibits leukocyte adhesion. J Inflamm (Lond). 2008 May 20;5:6.
2. Mathison RD, Davison JS. The Tripeptide feG Regulates the Production of Intracellular Reactive Oxygen Species by Neutrophils. J Inflamm (Lond). 2006 Jun 15;3(1):9
It makes me think that it is just a matter of time before we identify other relatively simple substances that exist within biological systems and have immune-modulatory properties...fascinating, indeed!
ReplyDeleteI would participate in a human study. I believe this could be a cure for Hashimoto! freedomflagfly@yahoo.com
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