Immune Selective Anti-Inflammatory Derivatives (ImSAIDs) are a class of

peptides Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

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.

History

The ImSAIDs represent a new category of anti-inflammatory and are unrelated to

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

hormones or non steroidal anti-inflammatories. The ImSAIDs were discovered by scientists evaluating biological properties of the

submandibular gland The paired submandibular glands (historically known as submaxillary glands) are major salivary glands located beneath the floor of the mouth. They each weigh about 15 grams and contribute some 60–67% of unstimulated saliva secretion; on stimula ...

and

saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...

. 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. 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 The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...

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. 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. 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,.

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 Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

- glutamine- glycine (FEG) and its D-

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

ic form (feG), have become the foundation for the ImSAID category.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.

References

{{DEFAULTSORT:Immune-Selective Anti-Inflammatory Derivative Anti-inflammatory agents