Antisense (AS) peptides complementary to the beta-bulge surface loop VQGEESNDK (Boraschi loop) of the cytokine interleukin-1beta (IL-1beta) have been shown to bind IL-1beta at the Boraschi loop position, and to inhibit some of the IL-1beta-mediated biological effects in vitro. Here we show that primary AS peptide FVITFFSLY inhibits IL-1beta-mediated immunostimulation in vivo in a dose-dependent fashion, while inactive on IL-1beta-induced inflammation, an effect that takes place independently of the Boraschi loop. To the best of our knowledge, this is the first time that an AS peptide has been used successfully in vivo.