Triggering receptor expressed on myeloid cells-1 (TREM-1) is expressed on innate immune cells and plays a crucial role during the onset of sepsis by amplifying the host immune response. TREM-like transcript-1 (TLT-1) belongs to the TREM family and is selectively expressed on activated platelets. We recently showed that TLT-1 and a TLT-1-derived peptide (LR12) exhibit anti-inflammatory properties by dampening TREM-1 signalling and thus behave as naturally occurring TREM-1 inhibitors . We also, however, demonstrated that the same peptide modulates in vivo the inflammatory cascade triggered by infection, thus inhibiting hyper-responsiveness, organ damage and death during sepsis in mice. As mouse models of septic shock are far from recapitulating the human physiology, we investigated the effects of LR12 during peritonitis in adult mini-pigs. Here we show that sepsis-induced cardiovascular dysfunction and organ failure was prevented by LR12 administration. The objective was to determine the effects of a TLT-1 derived peptide (LR12) administration during septic shock in pigs (13 adult male mini-pigs).