Immune Selective Anti-Inflammatory Derivatives (ImSAIDs) are a class of peptides that have anti-inflammatory properties. ImSAIDs work by altering the activation and migration of inflammatory cells, which are immune cells responsible for amplifying the inflammatory response.[1][2]

History

The ImSAIDs represent a new category of anti-inflammatory and are unrelated to steroid hormones or non steroidal anti-inflammatories. The ImSAIDs were discovered by scientists evaluating biological properties of the submandibular gland and saliva. Early work in this area demonstrated that the submandibular gland released a host of factors which regulate systemic inflammatory responses and modulate systemic immune and inflammatory reactions. Early work in identifying factors that played a role in the CST-SMG axis lead to the discovery of a seven amino acid peptide, called the submandibular gland peptide-T. SGP-T was demonstrated to have biological activity and thermoregulatory properties related to endotoxin exposure.[3] SGP-T, an isolate of the submandibular gland, demonstrated its immunoregulatory properties and potential role in modulating the cervical sympathetic trunk-submandibular gland (CST-SMG) axis, and subsequently was shown to play an important role in the control of inflammation.

Mechanisms or ImmunoPharmacology

It is now well accepted that the immune, nervous and endocrine systems communicate and interact to control and modulate inflammation and tissue repair. One of the neuroendocrine pathways, when activated, results in the release of immune regulating peptides from the submandibular gland upon neuronal stimulation from sympathetic nerves. This pathway or communication is referred to as the cervical sympathetic trunk-submandibular gland (CST-SMG) axis, a regulatory system that plays a role in the systemic control of inflammation.[4]

Cellular Effects of feG: The cellular effects of the ImSAIDs are characterized in a number of publications. feG and related peptides are known to modulate leukocyte (white blood cells) activity by influencing cell surface receptors to inhibit excessive activation and tissue infiltration. One lead ImSAID, the tripeptide FEG (Phe-Glu-Gly) and its D-isomer feG are known to alter leukocyte adhesion involving actions on αMβ2 integrin, and inhibit the binding of CD16b (FCyRIII) antibody to human neutrophils.[5] One ImSAID, termed feG, has also been shown to decrease circulating neutrophil and eosinophil accumulation, decrease intracellular oxidative activity and reduced the expression of CD49d after antigen exposure,.[6][7][8]

Lead Compound

One SGP-T derivative is a three amino acid sequence shown to be a potent anti-inflammatory molecule with systemic effects. This three amino acid peptide is phenylalanine-glutamine-glycine (FEG) and its D-isomeric form (feG), have become the foundation for the ImSAID category.[9]

References

  1. ↑ Bao, F; John, SM; Chen, Y; Mathison, RD; Weaver, LC (2006). "The tripeptide phenylalanine-(D) glutamate-(D) glycine modulates leukocyte infiltration and oxidative damage in rat injured spinal cord". Neuroscience. 140 (3): 1011–22. doi:10.1016/j.neuroscience.2006.02.061. PMID 16581192.
  2. ↑ Mathison, RD; Befus, AD; Davison, JS; Woodman, RC (Mar 2003). "Modulation of neutrophil function by the tripeptide feG". BMC Immunol. 4: 3. doi:10.1186/1471-2172-4-3. PMC 152650. PMID 12659660.
  3. ↑ Mathison, RD; Malkinson, T; Cooper, KE; Davison, JS (May 1997). "Submandibular glands: novel structures participating in thermoregulatory responses". Can J Physiol Pharmacol. 75 (5): 407–13. doi:10.1139/y97-077. PMID 9250374.
  4. ↑ Mathison, R; Davison, JS; Befus, AD (Nov 1994). "Neuroendocrine regulation of inflammation and tissue repair by submandibular gland factors". Immunol Today. 15 (11): 527–32. doi:10.1016/0167-5699(94)90209-7. PMID 7802923.
  5. ↑ Mathison, RD; Christie, E; Davison, JS (May 2008). "The tripeptide feG inhibits leukocyte adhesion". J Inflamm (Lond). 5: 6. doi:10.1186/1476-9255-5-6. PMC 2408570. PMID 18492254.
  6. ↑ Dery, RE; Ulanova, M; Puttagunta, L; Stenton, GR; James, D; Merani, S; Mathison, R; Davison, J; Befus, AD (Dec 2004). "Frontline: Inhibition of allergen-induced pulmonary inflammation by the tripeptide feG: a mimetic of a neuro-endocrine pathway". Eur J Immunol. 34 (12): 3315–25. doi:10.1002/eji.200425461. PMID 15549777.
  7. ↑ Mathison, RD; Davison, JS (Jun 2006). "The Tripeptide feG Regulates the Production of Intracellular Reactive Oxygen Species by Neutrophils". J Inflamm (Lond). 3 (1): 9.
  8. ↑ Mathison, R; Lo, P; Tan, D; Scott, B; Davison, JS (Dec 2001). "The tripeptide feG reduces endotoxin-provoked perturbation of intestinal motility and inflammation". Neurogastroenterol Motil. 13 (6): 599–603. doi:10.1046/j.1365-2982.2001.00294.x. PMID 11903921.
  9. ↑ Dery RE, Mathison R, Davison J, Befus AD. "Inhibition of allergic inflammation by C-terminal peptides of the prohormone submandibular rat 1 (SMR-1). Int Arch Allergy Immunol. 2001 an-Mar;124(1-3):201-4.
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