Findings suggest that severe sepsis can lead to impairment of immune system
An analysis of lung and spleen tissue from patients who died of sepsis revealed certain biochemical, cellular and histological findings that were consistent with immunosuppression, according to a study in the December 21 issue of JAMA.
"Sepsis is responsible for more than 225,000 deaths annually in the United States. Developing new therapies for sepsis has been particularly challenging, with more than 25 unsuccessful drug trials. Characterized by an initial intense inflammatory response or 'cytokine storm,' patients with sepsis may present with fever, shock, altered mental status, and organ dysfunction," according to background information in the article. "Whether this hyperinflammatory phase is followed by immunosuppression is controversial. Animal studies suggest that multiple immune defects occur in sepsis, but data from humans remain conflicting."
Jonathan S. Boomer, Ph.D., of the Washington University School of Medicine, St. Louis, and colleagues conducted a study to assess evidence of immunosuppression in sepsis and to determine mechanisms that might be responsible for the presumed impaired immunity. For the study, to characterize their immune status at the time of death (2009-2011), postmortem spleen and lung tissue harvest was performed on 40 patients who died in intensive care units (ICUs) with active severe sepsis. Control spleens (n = 29) were obtained from patients who were declared brain-dead or had emergency splenectomy due to trauma; control lungs (n = 20) were obtained from transplant donors or from lung cancer resections. Various tests were performed on the tissue samples to identify potential mechanisms of immune dysfunction.
The average ages of patients with sepsis and controls were 72 and 53 years, respectively. The median (midpoint) number of ICU days for patients with sepsis was 8, while control patients were in ICUs for 4 or fewer days. The median duration of sepsis was 4 days. Among the results of the researchers were that patients who died of sepsis had biochemical, flow cytometric (cell analysis), and immunohistochemical (process of detecting antigens in cells of a tissue section) findings that were consistent with immunosuppression, compared with the patients who died of nonsepsis causes.
"The present study has a number of important therapeutic implications. Most investigative agents in sepsis have been directed at blocking inflammation and immune activation. Although such therapies may be successful if applied early, they may be harmful if applied later in the immunosuppressive phase. As supportive therapies of sepsis have improved, early deaths have decreased and most patients enter a more protracted phase, with evidence of impaired immunity made manifest by infections with relatively avirulent organisms. An important part of implementing more targeted therapies will be to accurately determine the immune status of individual patients during their disease," the authors write.
Peter A. Ward, M.D., of the University of Michigan Medical School, Ann Arbor, comments on the findings of this study in an accompanying editorial.
"Boomer and colleagues have presented an informative report documenting immunosuppression in humans with septic shock, along with the broad array of cellular changes that can be linked to the loss of immune competence. A next step might be to determine why during sepsis immune cells switch from a phenotype with proimmuue receptors and ligands to a phenotype featuring anti-immune receptors and ligands. Another important research question is whether such derangements in sepsis involving humans can be reversed by treatment with agents such as interleukins 7 or 15. These agents in some settings may restore immune responsiveness by increasing the number of competent T cells."
More information: JAMA. 2011;306:2594-2605.
Provided by JAMA and Archives Journals
- BUSM: Severe sepsis, new-onset AF associated with increased risk of hospital stroke, death Nov 13, 2011 | not rated yet | 0
- Nationwide trends for sepsis in the 21st century Aug 18, 2011 | not rated yet | 0
- Surprising interactions of diabetes mellitus and sepsis Feb 13, 2009 | not rated yet | 0
- Sepsis guideline compliance improves, rate of death declines after educational effort May 20, 2008 | not rated yet | 0
- Researchers announce discovery in fight against sepsis Jul 11, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Calculating on-axis elements of a solenoid
6 hours ago I wanted to mention that this solenoid has many winds over many layers. The thickness of the windings is 2.4 inches coming off of the engineering...
latitude & longitude & air pressure
8 hours ago Hi there, I have a peculiar question. Imagine that you are in a earth position, obtained by google, that gives you the latitude and longitude....
Differences of Classical Mechanics when learned with Calc vs algebra?
11 hours ago what are the differences? Every example I find usually has a derivative or integral or some kind of calculus defined concept that seems to make it...
what is the distance traveled
15 hours ago A rough sketch of experiment. Image: http://i43.tinypic.com/14t4sk5.png the red dots represent a side view of path traveled, F is downward force...
Image of a Convex Lens Cut in Half Horizontally
19 hours ago Hello everyone, A friend of mine came up with this question in class and I really do not have a good answer. Suppose you have a convex lens...
Ray tracing through optical system of thick lenses
19 hours ago Can you advise me a free software that allow to draw rays passed throught system of thick lenses (preferable in 3D)?
- More from Physics Forums - Classical Physics
More news stories
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
Immunology May 20, 2013 | 4.8 / 5 (24) | 8 |
(Medical Xpress)—Scientists at King's College London have discovered that Vitamin D has the potential to significantly reduce the symptoms of asthma. The study, led by Professor Catherine Hawrylowicz from ...
Immunology May 20, 2013 | 5 / 5 (1) | 0 |
Melbourne researchers have identified an immune protein that has the potential to stop or reverse the development of type 1 diabetes in its early stages, before insulin-producing cells have been destroyed.
Immunology May 20, 2013 | 5 / 5 (5) | 0 |
Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory. The researchers showed that, in mice, ...
Immunology May 16, 2013 | 4.8 / 5 (5) | 0 |
Researchers from CNRS, Université Toulouse III - Paul Sabatier and IRD have elucidated new molecular mechanisms involved in resistance to visceral leishmaniasis, a serious parasitic infection. They have shown that dectin-1 ...
Immunology May 16, 2013 | not rated yet | 0
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
15 hours ago | 4.9 / 5 (7) | 0 |
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
15 hours ago | 4.7 / 5 (3) | 0 |
Existing research shows that bicyclists who wear helmets have an 88 percent lower risk of brain injury, but researchers at Boston Children's Hospital found that simply having bicycle helmet laws in place showed a 20 percent ...
4 hours ago | not rated yet | 0
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
12 hours ago | 5 / 5 (2) | 2 |
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
11 hours ago | 4 / 5 (2) | 0 |
A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...
12 hours ago | not rated yet | 0 |