Biomarkers of early sepsis may be correlated with outcome.

BACKGROUND: Sepsis causes high mortality, and the mortality due to secondary infections is even higher. No studies to date have investigated the time from the primary infection to death due to a secondary infection; similarly, the factors that are significantly different in sepsis survivors relative to non-survivors or in severe sepsis patients who suffered a late death relative to those who recover have not been explored. We hypothesized that patients who survive sepsis have a weaker pro-inflammatory response than those who do not and that the mid-term survivors (which acquire secondary infections) would have a pronounced anti-inflammatory response (making them susceptible to infection); this hypothesis was verified in this study. METHODS: We examined 24 patients with severe sepsis; the patients were subdivided by outcome into early death (n=5), mid-term survival (survival through severe sepsis but death within six months or continued hospitalization for six months, n=6), and long-term survival (recovery and survival for more than six months, n=13) groups. The levels of CD3+, CD4+, CD8+, and CD19+ lymphocytes were analyzed by flow cytometry, and the plasma levels of carbonic anhydrase IX (CA IX), MCP-1, IL-6, IL-7, IL-8, and IL-10 were measured by ELISA on days 0, 1, 2, and 3. A statistical comparison of the variables in the groups was conducted using a mixed model. RESULTS: The plasma levels of MCP-1, IL-6, and IL-8 in early death and survivors were significantly different, and all had p values<0.01. The plasma levels of MCP-1, IL-6, and IL-8 were also significantly different in mid-term survivors and long-term survivors, with p values of <0.01, 0.04, and <0.01, respectively. CONCLUSIONS: Our data support the hypothesis that survivors have a weaker pro-inflammatory response than non-survivors, but the mid-term survivors did not have a more pronounced anti-inflammatory response. The levels of pro-inflammatory cytokines in the mid-term and long-term survivors were significantly different.

Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression.

Macrophages in a tumor microenvironment have been characterized as M1- and M2-polarized subtypes. Here, we discovered the different macrophages' impacts on lung cancer cell A549. The M2a/M2c subtypes promoted A549 invasion and xenograft tumor growth. The M1 subtype suppressed angiogenesis. M1 enhanced the sensitivity of A549 to cisplatin and decreased the tube formation activity and cell viability of A549 cells by inducing apoptosis and senescence. Different macrophage subtypes regulated genes involved in the immune response, cytoskeletal remodeling, coagulation, cell adhesion, and apoptosis pathways in A549 cells, which was a pattern that correlated with the altered behaviors of the A549 cells. Furthermore, we found that the identified M1/M2 gene signatures were significantly correlated with the extended overall survival of lung cancer patients. These results suggest that M1/M2 gene expression signature may be used as a prognostic indicator for lung cancer patients, and M1/M2 polarization may be a target of investigation of immune-modulating therapies for lung cancer in the future.

Do interleukin-10 and superoxide ions predict outcomes of cardiac extracorporeal membrane oxygenation patients?

Extracorporeal membrane oxygenation (ECMO) is used for cardiogenic shock rescue. It is hard to predict the outcome from this treatment by clinical observation in days soon after installation. We analyzed the plasma levels of interleukin (IL)-6, IL-8, IL-10, reactive oxygen species, and 8-OHdG, and the glutathione peroxidase activities from 23 cases at the time of ECMO installation before resuscitation. Generalized additive models (GAM) were performed to identify the death ranges of every variable, and the variables were further discretized. The impaired release of IL-10 on shock led to death. IL-10 levels at >16.58 pg/ml differentiated death from survival for acute myocardial infarction (AMI) patients, and levels at >143.17 pg/ml did the same for dilated cardiomyopathy (DCMP) patients. The prediction power of discretized IL-10 alone was measured as area under the curve (AUC) 0.913. The generalized linear model was then performed to predict the best composition from both the original and discretized variables and resulted in AUC 0.97 for the combined discretized IL-10 and superoxide ions. Two missed myocarditis cases from IL-10 prediction were resolved by superoxide ion levels. Our observations lead to the hypothesis that a proper response to cardiogenic shock by releasing the appropriate amount of IL-10 is required for survival in the cases of AMI and DCMP. For myocarditis, proper responses in IL-10 and superoxide ions are needed.