Use: Immune-and inflammation-mediated diseases, such as arthritis, asthma, dermatitis and inflammatory bowel disease, are difficult to treat. The large and complex DNA viruses, such as herpesviruses and poxviruses, have developed highly effective mechanisms for blocking and evading host immune responses to cellular invasion, often by secreting proteins that modulate pivotal points in inflammatory and immune responses.[1, 2] The viral immunomodulatory proteins discovered to date include complement and growth factor regulators, cytokine and cytokine receptor mimics, and serine proteinase inhibitors (serpins). We are exploiting the capability of these secreted proteins, even in the absence of virus infection, to develop new therapeutic agents designed to inhibit excessive immune and inflammatory activity.

History: Our 2 laboratories have collaborated to create an innovative technology designed to assess purified, secreted viral proteins as novel anti-inflammatory reagents. 3 After the discovery of multiple myxoma virus virulence factors that protect the virus from clearance by inflammatory cells, 4 a serpin, designated SERP-1, was tested in a rabbit model of angioplasty-mediated injury. 3 Atherosclerotic plaque development was markedly reduced after a single injection of picogram to nanogram doses of SERP-1 given immediately after surgery (Figure). 3 This correlated with reduced counts of monocytes and macrophages invading the damaged arterial wall within the first 2 days after angioplasty. 3 In subsequent pilot studies SERP-1 was also effective in significantly reducing joint erosion in rabbit and rat models of collagen-induced arthritis [5, 6] and plaque development in a rat aortic allograft model of transplant vasculopathy.[7, 8]