National Hansen's Disease Program

Research Interests: Edward J. Shannon

Erythema nodosum leprosum (ENL) is an inflammatory complication that can occur in multibacillary HD patients. The treatment of choice is thalidomide. The sequence of events, which cause ENL as well as the mechanism(s) by which thalidomide and/or steroids arrest ENL have not been elucidated.

In clinical trials and sepsis studies in rodents, thalidomide is able to augment or to suppress the synthesis of inflammatory cytokines, especially TNF-alpha. Consequently, interpretation of the literature regarding thalidomide’s ability to regulate the “cytokine storm” in inflammatory conditions is confusing.

My research efforts are to determine thalidomide’s effect on three major cytokines, TNF-alpha, IL-6 and IL-8. These are involved in systemic inflammatory response syndromes. I am also interested in investigating a role for thalidomide in antibody synthesis and activation of complement. This is based on evidence that antibody and complement may be involved in the ENL reaction, and recent observations that thalidomide, in combination with dexamethasone, has a therapeutic effect on patients with multiple myeloma, a condition in which immunoglobulin synthesis continues unabated. In collaboration with investigators in the Research Branch and other institutions, we are studying the effect of thalidomide on various functions of schwann cells. This is based on reports that continuous use of thalidomide, especially in treating conditions other than ENL, can induce neuritis.

Representative Publications

Tadesse, A., Shannon, E.J. Effects of thalidomide on intracellular Mycbacterium leprae in normal and activated macrophages. Clinical and Diagnostic Laboratory Immunology 12(1): 30-134, 2005.

Tadesse,A., Abebe, M.,Bizuneh, E., M., A. Aseffa, Shannon, E.J. The effect of thalidomide on the expression of TNF mRNA and the synthesis of TNF in cells from leprosy patients with reversal reaction. Immunopharmacology and Immunotoxicology, 28:1-11,2006.