IMULAN BioTherapeutics, LLC, is a veterinary immunobiology company developing a range of immune based therapies for veterinary medicine. IMULAN BioTherapeutics, LLC has several divisions related to immuno-biology and comparative medicine. IMULAN Clinical Trials, a clinical trial division of IMULAN BioTherapeutics, conducts a variety of comparative disease trials in oncology, asthma, sepsis, cardiology, and virology.
Immune Selective Anti-Inflammatory Derivativesimsaids - small peptides which regulate granulocyte function, modulate neutrophil chemotaxis and activation, reduce the production of reactive oxygen species, and reduce the effects of endotoxin. Immune Selective Anti-Inflammatory Derivatives (ImSAIDs) are a class of peptides discovered to have diverse biological properties, including remarkable anti-inflammatory properties. ImSAIDs work by altering the activation and migration of inflammatory cells, which are immune cells responsible for amplifying the inflammatory response. 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. 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. Early work in identifying factors that played a role in the CST-SMG axis lead to the discovery of a seven amino acidpeptide, 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. One SGP-T derivative is a three amino acid sequence shown to be a potent anti-inflammatorymolecule 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. 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. 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.
^Bao F, John SM, Chen Y, Mathison RD, Weaver LC. The tripeptide phenylalanine-(D) glutamate-(D) glycine modulates leukocyte infiltration and oxidative damage in rat injured spinal cord. Neuroscience. 2006 Jul 7;140(3):1011-22. Epub 2006 Apr 3.
^Mathison RD, Befus AD, Davison JS, Woodman RC. Modulation of neutrophil function by the tripeptide feG. BMC Immunol. 2003 Mar 4;4:3. Epub 2003 Mar 4
^Mathison R, Davison JS, Befus AD. Neuroendocrine regulation of inflammation and tissue repair by submandibular gland factors. Immunol Today. 1994 Nov;15(11):527-32. Review.
^Mathison RD, Malkinson T, Cooper KE, Davison JS. Submandibular glands: novel structures participating in thermoregulatory responses. Can J Physiol Pharmacol. 1997 May;75(5):407-13.
^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.
^Mathison RD, Christie E, Davison JS. The tripeptide feG inhibits leukocyte adhesion. J Inflamm (Lond). 2008 May 20;5:6.
^Dery RE, Ulanova M, Puttagunta L, Stenton GR, James D, Merani S, Mathison R, Davison J, Befus AD. Frontline: Inhibition of allergen-induced pulmonary inflammation by the tripeptide feG: a mimetic of a neuro-endocrine pathway. Eur J Immunol. 2004 Dec;34(12):3315-25
^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
^Mathison R, Lo P, Tan D, Scott B, Davison JS. The tripeptide feG reduces endotoxin-provoked perturbation of intestinal motility and inflammation. Neurogastroenterol Motil. 2001 Dec;13(6):599-603.