Prophylactic Treatment With Simvastatin Modulates the Immune Response and Increases Animal Survival Following Lethal Sepsis Infection.

Chronic use of statins may have anti-inflammatory action, promoting immunomodulation and survival in patients with sepsis. This study aimed to analyze the effects of pretreatment with simvastatin in lethal sepsis induced by cecal ligation and puncture (CLP). Male Swiss mice received prophylactic treatment with simvastatin or pyrogen-free water orally in a single daily dose for 30 days. After this period, the CLP was performed. Naïve and Sham groups were performed as non-infected controls. Animal survival was monitored for 60 h after the CLP. Half of mice were euthanized after 12 h to analyze colony-forming units (CFUs); hematological parameters; production of IL-10, IL-12, IL-6, TNF-α, IFN-γ, and MCP-1; cell counts on peritoneum, bronchoalveolar lavage (BAL), bone marrow, spleen, and mesenteric lymph node; immunephenotyping of T cells and antigen presenting cells and production of hydrogen peroxide (H2O2). Simvastatin induced an increase in survival and a decrease in the CFU count on peritoneum and on BAL cells number, especially lymphocytes. There was an increase in the platelets and lymphocytes number in the Simvastatin group when compared to the CLP group. Simvastatin induced a greater activation and proliferation of CD4+ T cells, as well as an increase in IL-6 and MCP-1 production, in chemotaxis to the peritoneum and in H2O2 secretion at this site. These data suggest that simvastatin has an impact on the survival of animals, as well as immunomodulatory effects in sepsis induced by CLP in mice.

Chenopodium ambrosioides L. Improves Phagocytic Activity and Decreases Bacterial Growth and the Systemic Inflammatory Response in Sepsis Induced by Cecal Ligation and Puncture.

Chenopodium ambrosioides L. (Amaranthaceae) is often used in different kinds of vegetal preparations for medicinal purposes in many clinical situations. Some studies have demonstrated its anti-inflammatory and immunomodulatory properties. The aim of this work was to investigate the effect of prophylactic treatment with the hydroalcoholic crude extract (HCE) of C. ambrosioides and its hexanic fraction (HEX) on the control of bacterial growth, the activation of phagocytes and the control of the systemic inflammatory response in a sepsis experimental model. Animals were divided into three groups (n = 5/group): Control, which received only NaCl 0.9% solution; HCE, which received the crude extract; and HEX, which received the HEX of the extract. The animals received saline, HCE or HEX (5 mg/kg), subcutaneously (SC), 6 h before cecal ligation and puncture (CLP). Twelve hours after the CLP, the blood was collected to measure the serum cytokines and the animals were killed for the evaluation of colony-forming units (CFUs), cellular influx, and activation of phagocytes in the peritoneal cavity, measured by the secretion of hydrogen peroxide and nitric oxide production. The results showed that only HEX treatment inhibited bacterial growth in the peritoneum and inflammatory cellular influx, especially influx of macrophages and neutrophils. However, HCE and HEX treatments increased ex vivo hydrogen peroxide secretion and nitric oxide production by phagocytes and decreased the pro-inflammatory cytokines in the serum, indicating a systemic anti-inflammatory effect of both. In conclusion, C. ambrosioides treatment decreases bacterial growth likely by activation of phagocytes and, in parallel, ameliorates the general state of mice by reducing the systemic inflammatory response usually observed in sepsis.