Findings suggest that severe sepsis can lead to impairment of immune system

December 20, 2011, JAMA and Archives Journals

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 or 'cytokine storm,' patients with sepsis may present with fever, shock, altered mental status, and ," 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 and 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 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 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 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."

Explore further: BUSM: Severe sepsis, new-onset AF associated with increased risk of hospital stroke, death

More information: JAMA. 2011;306[23]:2594-2605.
JAMA. 2011;306[23]:2618-2619.

Related Stories

BUSM: Severe sepsis, new-onset AF associated with increased risk of hospital stroke, death

November 13, 2011
A recent study led by researchers at Boston University School of Medicine (BUSM) shows an increased risk of stroke and mortality among patients diagnosed with severe sepsis and new-onset atrial fibrillation (AF) during hospitalization.

Nationwide trends for sepsis in the 21st century

August 18, 2011
Severe sepsis is common and often fatal, although evidence-based therapies have improved patient outcomes.

Researchers announce discovery in fight against sepsis

July 11, 2011
New research from the Trudeau Institute may help to explain why anticoagulant therapies have largely failed to extend the lives of patients with sepsis. The study was led by Deyan Luo, a postdoctoral fellow in Stephen Smiley's ...

Quicker detection and treatment of severe sepsis

May 23, 2011
Sepsis is the name of an infection that causes a series of reactions in the body, which in the worst case can prove fatal. The problem for both patients and doctors is that the early symptoms are difficult to distinguish ...

Recommended for you

Researchers discover key driver of atopic dermatitis

January 17, 2018
Severe eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition that is driven by an allergic reaction. In their latest study, researchers at La Jolla Institute reveal an important player that promotes ...

Who might benefit from immunotherapy? New study suggests possible marker

January 16, 2018
While immunotherapy has made a big impact on cancer treatment, the fact remains that only about a quarter of patients respond to these treatments.

Researchers identify new way to unmask melanoma cells to the immune system

January 16, 2018
system, which enables these deadly skin cancers to grow and spread.

How the immune system's key organ regenerates itself

January 15, 2018
With advances in cancer immunotherapy splashing across headlines, the immune system's powerful cancer assassins—T cells—have become dinner-table conversation. But hiding in plain sight behind that "T" is the organ from ...

Immunosuppressive cells in newborns play important role in controlling inflammation in early life

January 15, 2018
New research led by The Wistar Institute, in collaboration with Sun Yat-sen University in China, has characterized the transitory presence of myeloid-derived suppressor cells (MDSCs) in mouse and human newborns, revealing ...

Memory loss from West Nile virus may be preventable

January 15, 2018
More than 10,000 people in the United States are living with memory loss and other persistent neurological problems that occur after West Nile virus infects the brain.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.