Pneumonia is associated with elevated concentrations of the proinflammatory cytokine interleukin (IL)-1 in the pulmonary compartment. To study the role of IL-1 in the pathogenesis of Pseudomonas pneumonia, IL-1 receptor type 1 gene-deficient (IL-1R -/-) mice and wild-type mice were intranasally inoculated with Pseudomonas aeruginosa. The absence of the IL-1 signal attenuated the outgrowth of Pseudomonas in lungs, as reflected by an increasing number of colony-forming units (cfu) during Pseudomonas pneumonia in wild-type mice and a concurrently decreasing number of cfu during pulmonary infection in IL-1R -/- mice (P < 0.05, IL-1R -/- mice vs. wild-type mice). Influx of neutrophils was decreased in bronchoalveolar lavage fluids in IL-1R -/- mice compared with wild-type mice. Similarly, lung levels of cytokines (tumor necrosis factor-alpha, IL-6) and chemokines (macrophage inflammatory protein-2 and KC) were lower in IL-1R -/- mice 24 h postinoculation. Consistent with results obtained in IL-1R -/- mice, treatment of wild-type mice with IL-1R antagonist also diminished outgrowth of Pseudomonas when compared with wild-type mice treated with vehicle (P < 0.05). These results demonstrate that an absence or reduction in endogenous IL-1 activity improves host defense against Pseudomonas pneumonia while suppressing the inflammatory response.
Achieving adequate glucose control in critically ill patients is a complex but important part of optimal patient management. Until relatively recently, intermittent measurements of blood glucose have been the only means of monitoring blood glucose levels. With growing interest in the possible beneficial effects of continuous over intermittent monitoring and the development of several continuous glucose monitoring (CGM) systems, a round table conference was convened to discuss and, where possible, reach consensus on the various aspects related to glucose monitoring and management using these systems. In this report, we discuss the advantages and limitations of the different types of devices available, the potential advantages of continuous over intermittent testing, the relative importance of trend and point accuracy, the standards necessary for reporting results in clinical trials and for recognition by official bodies, and the changes that may be needed in current glucose management protocols as a result of a move towards increased use of CGM. We close with a list of the research priorities in this field, which will be necessary if CGM is to become a routine part of daily practice in the management of critically ill patients.
p38 mitogen-activated protein kinase (MAPK) has been suggested as a mediator of cytokine release and is currently being targeted for anti-inflammatory therapy. However, experimental data are contradictory and lack sufficient affirmation in vivo. We tested the effect of p38 MAPK inhibition in several cell types and in different murine models of infectious disease. We observed that most cell types react to p38 MAPK inhibition with diminished cytokine release, but that this treatment induced increased cytokine release in macrophages. Furthermore, we observed increased cytokine production in mouse models of pneumococcal pneumonia and tuberculosis accompanied by severely reduced bacterial clearance. This apparent inefficacy of p38 MAPK inhibition in reducing cytokine release in infectious disease, as well as its immune-compromising action, suggest that targeting p38 MAPK may not be a suitable anti-cytokine strategy in patients with such disease or at risk for infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.