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Sepsis is a systemic inflammatory response resulting from the inability of the host to restrict the infection locally. Studies realized in our laboratory demonstrated that the high mortality observed in severe sepsis (S-CLP) correlates with the failure of the neutrophil migration to infectious focus and infection dissemination. However, animals subjected to a model of local infection (NS-CLP) present an efficient neutrophil recruitment that constrains the spreading of infection. In this context, we demonstrated a direct action of IL-17 mediating the neutrophil recruitment [1]. Recently, it was demonstrated that aryl hydrocarbon receptor (AhR) activation has a role in immune response. The AhR is expressed by Th17 cells and also by innate immune system cells and is important for their effectors functions, including IL-17 and IL-22 production [2]. However, the function of the AhR in sepsis remains uncertain. Herein, we investigate the role of AhR in polymicrobial sepsis induced by cecal ligation and puncture (CLP).

AB103 is a novel CD28 antagonist peptide currently in clinical development that modulates CD28 signaling in T cells, without affecting the normal humoral immune response. In experimental models of Gram-positive, Gram-negative and polymicrobial sepsis, AB103 demonstrated significant activity, increasing overall survival.

The impact of cytokine storm on plasma neutrophil gelatinase-associated lipocalin (NGAL) levels during polymicrobial sepsis is unknown. We demonstrate the advantage of plasma NGAL as marker for acute kidney injury (AKI) during septic cytokine storm and an early correlation of tumor necrosis factor alpha (TNFa) with NGAL during septic AKI.

In our previous studies we demonstrated that CXC chemokine receptor 3 (CXCR3) participates in the regulation of lymphocyte trafficking during cecal ligation and puncture (CLP)-induced sepsis. In this study, we evaluated the effects of treatment with anti-CXCR3 immunoglobulin (IgG) and antibiotics on outcome during septic shock caused by CLP.C57BL/6J mice were treated with neutralizing IgG against CXCR3 plus Primaxin either 24 hours prior to, 2 hours after or 6 hours after CLP. Control mice received nonspecific IgG plus Primaxin in the same regimen. Survival, core body temperature, bacterial clearance and systemic cytokine production were evaluated.Our results show that treatment with anti-CXCR3 IgG plus Primaxin significantly improved survival when administered 24 hours prior to CLP (50% vs. 10%), 2 hours after CLP (55% vs. 10%) or 6 hours after CLP (55% vs. 25%) compared with mice receiving nonspecific IgG plus Primaxin. Treatment with anti-CXCR3 plus Primaxin 24 hours prior to CLP attenuated hypothermia and IL-6 and macrophage inflammatory protein 2 (MIP-2) production but did not alter bacterial clearance. Treatment with anti-CXCR3 IgG and Primaxin 2 hours after CLP did not improve bacterial clearance and systemic cytokine production compared with mice treated with IgG and Primaxin, whereas 6 hours after CLP the bacterial clearance and IL-6 and MIP-2 concentrations, both in plasma and peritoneal lavage fluid, were significantly improved in mice receiving anti-CXCR3 IgG and Primaxin compared with mice that only received nonspecific IgG and Primaxin.The results from this study indicate that neutralization of CXCR3 prior to, 2 hours after or 6 hours after the initiation of CLP-induced septic shock improves survival and attenuates CLP-induced inflammation and physiologic dysfunction.

Polymicrobial sepsis is associated with immunosuppression caused by the predominance of anti-inflammatory mediators and profound loss of lymphocytes through apoptosis, and so deaths directly related to sepsis are twofold higher in polymycrobial sepsis. The aim of study is to compare unimicrobial versus polymicrobial sepsis as regards microbiology, complications, length of stay, mortality, factor affecting mortality.

Peritonitis is the prototype of polymicrobial sepsis with kinetics of bacterial growth differing from those of other infections leading to sepsis. The effect of the extent of leaking of gut content in the response of the host was studied.

Introduction Dehydroepiandrosterone (DHEA) improves survival after trauma and sepsis, while mechanisms of action are not yet fully understood. Therefore, we investigated the influence of DHEA on local cytokine expression in a two-hit model. Methods Male NMRI mice were subjected to femur fracture/hemorrhagic shock and subsequent sepsis. Sham-operated animals were used as controls. DHEA (25 mg/kg) or vehicle was administered daily. Mortality rate, activity and body temperature were determined daily after sepsis induction. TNF-α, IL-1β and IL-10 mRNA expression pattern were investigated in lung and liver tissue after 48 and 96 hours. Results DHEA treatment resulted in a significantly reduced mortality rate and improvements in the clinical status. On cytokine level, only TNF-α was significantly reduced in the cecal ligation and puncture (CLP)-vehicle group in both tissues after 48 hours. This suppression could be restored by DHEA administration. In contrast, after 96 hours, TNF-α was up-regulated in the CLP-vehicle group while remaining moderate by DHEA treatment in liver tissue. Conclusions The improved outcome after DHEA treatment and trauma is coherent with restoration of TNF-α in liver and lung after 48 hours and a counter-regulatory attenuation of TNF-α in liver after 96 hours. Thus, DHEA seems to act, time and organ dependent, as a potent modulator of TNF-α expression.

The major cause of mortality and morbidity of patients and experimental animals with diabetes mellitus is sepsis due to their high susceptibility to microbial infections. However, the mechanisms involved in this increased susceptibility are unclear.

Sepsis is a systemic inflammatory response resulting from the inability of the host to contain the infection locally. We previously demonstrated that during severe sepsis there is a marked failure of neutrophil migration to the infection site, which contributes to dissemination of infection, resulting in high mortality. IL-17 plays an important role in neutrophil recruitment. Herein, we investigated the role of IL-17 receptor signaling in polymicrobial sepsis induced by cecal ligation and puncture (CLP).

Multiple organ dysfunction syndrome (MODS) frequently complicates sepsis contributing to poor outcome. Yet the evolution of MODS in the early septic mortality (ESM) is unclear. To delineate the ESM-MODS relationship, we compared the development and magnitude of organ injury between dying and surviving mice in the acute phase (days 1 to 5) of polymicrobial sepsis.

During severe sepsis a marked impairment of neutrophil migration into the infectious focus occurs, which is associated with dissemination of infection resulting in high mortality. We recently showed that heme oxygenase (HO) products, carbon monoxide and biliverdin, downregulate neutrophil recruitment by reducing the neutrophil/endothelium rolling and adhesion in a noninfectious inflammatory model. This study aimed to investigate a possible role of the HO-1 pathway on the failure of neutrophil recruitment in mice subjected to severe (S-CLP) polymicrobial sepsis induced by cecal ligation and puncture (CLP).