Using an animal model of endotoxemia, a condition in which there is a substantial increase in the levels of inflammatory cytokines and chemokines in serum, CGEN-25007 was shown to exhibit a profound and dose-dependent anti-inflammatory activity. In this study, the novel peptide was administered following the introduction of lipopolysaccharide (LPS), a bacterial substance that induces a strong response in the animal immune system leading to systemic inflammation.
The administration of CGEN-25007 resulted in a decrease of approximately 50% in the serum levels of inflammatory cytokines and chemokines, including tumor necrosis factor alpha, IL-6, interferon-gamma, MIP-1á and MIP-2. In addition, in ex-vivo experiments CGEN-25007 was found to strongly inhibit the secretion of inflammatory cytokines from human peripheral blood mononuclear cells (PBMCs) which had been challenged with LPS, staphylococcus epidermidis or anti-CD3 antibody, compounds known to activate the human immune system through different receptors.
PBMCs triggered with these compounds and treated with CGEN-25007 exhibited more than 80% inhibition of secretion of cytokines, including TNFá, IL-1á, IL-6, IL-8, IL-12 and MIP-1á. In addition, CGEN-25007 had only a 20% inhibitory effect on the secretion of GM-CSF and no effect on the secretion of IL-2, suggesting selectivity in the action of this peptide.
These results indicate that CGEN-25007 has immunosuppressive effects and therapeutic potential for the treatment of various inflammatory diseases and other immune related pathologies.