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May 19, 2011
 |  BC Innovations  |  Targets & Mechanisms

Thyroxine: MIFfed about sepsis

A U.S. research team has shown that d-thyroxine, an old hyperlipidemia drug from Abbott Laboratories,promotes survival in mouse models of sepsis by inhibiting the proinflammatory cytokine MIF.1 The team is planning a clinical trial of the drug to treat sepsis, but a better approach may be to develop thyroxine analogs.

Macrophage migration inhibitory factor (MIF) plays a key role in sepsis pathogenesis, and high serum levels of MIF in severe sepsis are associated with poor outcomes.2 Additionally, sepsis patients often have low serum levels of the thyroid hormone l-thyroxine (levothyroxine; T4), and these low levels are associated with severe disease and poor prognosis.3

Based on those two observations, a team led by Yousef Al-Abed hypothesized that MIF and l-thyroxine directly interact in sepsis. Supporting this hypothesis was a previous study by Al-Abed and colleagues at Yale School of Medicine showing that thyroxine shared a structural feature with a small molecule MIF antagonist called ISO-1.4

Al-Abed is professor of medicinal chemistry and director of the laboratory of medicinal chemistry at The Feinstein Institute for Medical Research and professor of molecular medicine at the Hofstra North Shore-LIJ School of Medicine at Hofstra University.

Now, his team has shown that high serum levels of MIF correlate with low l-thyroxine levels in severe sepsis patients and in rat models of the indication.

Molecular...

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