Hemopressin as an adjuvant treatment for sepsis Thayanne Brasil Barbosa Calcia1, Cyntia Pecli e Silva2, Rayzza Pessanha da Silva3, Bruno Jennings de Almeida3, Fernanda Barros Aragão4, Virginia Luiz de Sousa4, Leandro Araújo Lobo3, Claudia Pinto Figueiredo4, Claudia Farias Benjamim1 1Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro – UFRJ – Rio de Janeiro (RJ); 2Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro – UFRJ – Rio de Janeiro (RJ); 3Instituto de Microbiologia, Universidade Federal do Rio de Janeiro – UFRJ – Rio de Janeiro (RJ); 4Faculdade de Farmácia, Universidade Federal do Rio de Janeiro – UFRJ – Rio de Janeiro (RJ) Sepsis is defined as a dysregulated host response to infection associated with organs failure. The overwhelming production of proinflammatory cytokines at early stages followed by long-term immunosuppression leads to an increase in mortality and in the occurrence of secondary infections by opportunistic pathogens. Despite great advances in sepsis knowledge, there is still no efficient treatment capable to decrease mortality rates and to increase life quality in septic patients. Thus, the aim of our work is to study whether hemopressin (HP), a nonapeptide antagonist/inverse agonist of cannabinoid receptor 1, might function as an adjuvant treatment in a mouse model of sepsis. Our sepsis model was the cecal ligation and puncture (CLP), which consisted of the exposure and perforation of the cecum (9 perforations, 21G). Sham- operated mice were used as the surgery control group. Mice received antibiotic followed by HP 500 nmol/Kg or saline intraperitoneally, 5, 24, 48 and 72 h after surgery. Interestingly, HP treated CLP mice were not susceptible to Aspergillus fumigatus secondary infection, as opposed to CLP without treatment. Septic mice treated with HP seemed to have less cognitive impairment as observed in fear conditioning test. Another finding was the preservation of Peyer’s Patches in CLP operated animals treated with HP when compared with those who received saline. HP administration was capable of partially restore TCD4, TCD8 and B lymphocytes in the Peyer’ Patches and mesenteric lymph node of CLP animals. However, no changes in spleen dendritic cells and macrophages were found in both groups when compared with Sham. In in vitro analyses, neutrophils from naïve mice pretreated with HP and activated with LPS had an increase in proinflammatory cytokine production. However, we found that HP diminished NET and ROS production by human neutrophils stimulated with PMA. Taken together, our data suggest that HP can modulate efficiently innate immune response during sepsis, possibly avoiding T and B cells apoptosis. Still, HP seems to have direct activity on neutrophils, impairing the excessive ROS and NET production. Therefore, these HP effects impaired sepsis-induced immunosuppression.