Inflammation is part of an important mechanism triggered by the innate immune response that rapidly responds to invading
microorganisms and tissue injury. One important elicitor of the inflammatory response is the Gram-negative bacteria component
lipopolysaccharide (LPS), which induces the activation of innate immune response cells, the release of proinflammatory cytokines, such
as interleukin 1 and tumor necrosis factor (TNF-α), and the cellular generation of nitric oxide (NO) by the inducible nitric oxide synthase
(iNOS). Although essential to the immune response, uncontrolled inflammatory responses can lead to pathological conditions, such
as sepsis and rheumatoid arthritis. Therefore, identifying cellular targets for new anti-inflammatory treatments is crucial to improving
therapeutic control of inflammation-related diseases. More recently, the translation factor eIF5A has been demonstrated to have a proinflammatory
role in the release of cytokines and the production of NO. As eIF5A requires and essential and unique modification of a specific
residue of lysine, changing it to hypusine, eIF5A is an interesting cellular target for anti-inflammatory treatment. The present study
reviews the literature concerning the anti-inflammatory effects of inhibiting eIF5A function. We also present new data showing that the
inhibition of eIF5A function by the small molecule GC7 significantly decreases TNF-α release without affecting TNF-α mRNA levels.
We discuss the mechanisms by which eIF5A may interfere with TNF-α mRNA translation by binding to and regulating the function of
ribosomes during protein synthesis.