Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids

The possibility that glucocorticoids upregulate the expression of anti-infl ammatory mediators is an exciting prospect for therapy in inflammatory dise ases, because these molecules could give the therapeutic benefits of steroi ds without toxic side effects(1,2). Supernatants from monocytes' and macrop hages(4) cultured in the presence of glucocorticoids increase the dispersio n of neutrophils from a cell pellet in the capillary tube migration assay. This supernatant factor, unlike other neutrophil agonists, promotes dispers ive locomotion of neutrophils at uniform concentration, lowers their adhesi on to endothelial cells, inhibits their chemotactic response to fMLP and in duces distinctive morphological changes(5,6). Here we show that thymosin be ta 4 sulfoxide is generated by monocytes in the presence of glucocorticoids and acts as a signal to inhibit an inflammatory response. In vitro, thymos in beta 4 sulfoxide inhibited neutrophil chemotaxis, and in vivo, the oxidi zed peptide, but not the native form, was a potent inhibitor of carrageenin -induced edema in the mouse paw. Thymosin beta 4 is unique, because oxidati on attenuates its intracellular C-actin sequestering activity(7), but great ly enhances its extracellular signaling properties. This description of met hionine oxidation conferring extracellular function on a cytosolic proteins may have far-reaching implications for future strategies of anti-inflammat ory therapy.