The complex immune response associated with sepsis results in a high rate of morbidity and mortality, despite substantial basic science and clinical advances. Most of the research has centered on the innate immune response, in contrast to the adaptive immune system. This is likely caused by the perceived time frame during which these two responses are understood to mediate their effects. Interestingly, a large degree of lymphocyte apoptosis occurs within the first 24 h of septic insult, suggesting an earlier role for the adaptive response. As we outline, recent studies have shown that reducing T-cell apoptosis dramatically improves survival and bacterial clearance, likely through at least two mechanisms. First, the prevention of lymphocyte apoptosis can limit macrophage phagocytosis of dead T cells and the subsequent production of interleukin 10 and transforming growth factor-β. Second, T lymphocytes can generate interferon-γ and interleukin 17 within the first 24 h that can enhance the early innate immune function sufficient to blunt bacterial infection. However, these and other potent cytokines may have divergent effects that depend upon the severity of sepsis. In more severe sepsis models, activated T cells can increase sepsis morbidity and tissue injury. Conversely, in less severe models, functional T cells decrease mortality and bacterial load. Altogether, the mechanisms underlying protective versus pathological T-cell responses in sepsis remain to be elucidated. As the complex interplay between T cells and innate immune cells is elucidated, novel treatment and therapeutic strategies may be designed that allow for better outcomes in the management of sepsis.

A dysfunctional immune system is known to be part of the pathophysiology after burn trauma. However, reports that support this have used a variety of methods, with numerous variables, to induce thermal injury. We hypothesized that, all other parameters being equal, an injury infliction by a scald would yield different immunological responses than one inflicted by a flame. Here, we demonstrated that both burn methods produced a full-thickness burn, yet there was more of an increase in subdermal temperature, hematocrit, mortality, and serum IL-6 concentrations associated with the scald burn. On postinjury day 1, the scald-burned mice showed diminished lymphocyte numbers, interferon γ production, and lymphocyte T-bet expression as compared with sham- and flame-burned mice. On postburn day 8, spleens from both sets of thermally injured animals showed an increase in proinflammatory myeloid cells as compared with sham-burned mice. Furthermore, the T-cell numbers, T-bet expression, and phenotype were changed such that interferon γ production was higher in scald-burned mice than in sham- and flame-burned mice. Altogether, the data show that differential immunological phenotypes were observed depending on the thermal injury method used.

BackgroundThe immune response to trauma has traditionally been modeled to consist of the systemic inflammatory response syndrome (SIRS) followed by the compensatory anti-inflammatory response syndrome (CARS). We investigated these responses in a homogenous cohort of male, severe blunt trauma patients admitted to a University Hospital surgical intensive care unit (SICU). After obtaining consent, peripheral blood was drawn up to 96 hours following injury. The enumeration and functionality of both myeloid and lymphocyte cell populations were determined.ResultsNeutrophil numbers were observed to be elevated in trauma patients as compared to healthy controls. Further, neutrophils isolated from trauma patients had increased raft formation and phospho-Akt. Consistent with this, the neutrophils had increased oxidative burst compared to healthy controls. In direct contrast, blood from trauma patients contained decreased naïve T cell numbers. Upon activation with a T cell specific mitogen, trauma patient T cells produced less IFN-gamma as compared to those from healthy controls. Consistent with these results, upon activation, trauma patient T cells were observed to have decreased T cell receptor mediated signaling.ConclusionsThese results suggest that following trauma, there are concurrent and divergent immunological responses. These consist of a hyper-inflammatory response by the innate arm of the immune system concurrent with a hypo-inflammatory response by the adaptive arm.

Following burn injury, the host is susceptible to bacterial infections normally cleared by healthy patients. We hypothesized that during the systemic immune response that follows scald injury, the host's altered immune status increases infection susceptibility. Using a murine model of scald injury under inhaled anesthesia followed by intraperitoneal infection, we observed increased neutrophil numbers and function at postburn day (PBD) 1 compared with sham-burned and PBD4 mice. Further, increased mortality, bacteremia, and serum IL-6 were observed in PBD1 mice after Pseudomonas aeruginosa (PA) infection compared with sham-burned and PBD4 mice infected with PA. To examine these disparate responses, we investigated neutrophils isolated at 5 and 24 h following PA infection from PBD1 and sham-burned mice. Five hours after infection, there was no significant difference in number of recruited neutrophils; however, neutrophils from injured mice had decreased activation, active-p38, and oxidative burst compared with sham-burned mice. In direct contrast, 24 h after infection, we observed increased numbers, active-p38, and oxidative burst of neutrophils from PBD1 mice. Finally, we demonstrated that in neutrophils isolated from PBD1 mice, the observed increase in oxidative burst was p38 dependent. Altogether, neutrophil activation and function from thermally injured mice are initially delayed and later exacerbated by a p38-dependent mechanism. This mechanism is likely key to the observed increase in bacterial load and mortality of PBD1 mice infected with PA.

BackgroundAcute Kidney Injury results from pre renal, post renal or intrinsic renal causes. Reflex anuria is a very rare cause of renal impairment which happens due to irritation or trauma to one kidney or ureter, or severely painful stimuli to other nearby organs.Case PresentationHere we present a case of acute kidney injury secondary to reflex anuria in a patient who underwent extensive gynecological surgery along with ureteral manipulation which recovered spontaneously.ConclusionReflex Anuria is a rare and often not considered as cause of acute kidney injury. This case illustrates that this should be kept as a differential in potential cause of acute kidney injury in patient undergoing urogenital or gynecological surgeries.