We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Editor's Correspondence |

Mortality in Humans With Pneumonia and Sepsis Is Related to an Uncompensated Anti-inflammatory Response to Infection—Reply

John A. Kellum, MD; Derek C. Angus, MD, MPH
Arch Intern Med. 2008;168(13):1469. doi:10.1001/archinte.168.13.1469.
Text Size: A A A
Published online


In reply

We appreciate the comments of White and colleagues re garding our study characterizing the inflammatory cytokine response in pneumonia and sepsis.1 We certainly agree that classifying any cytokine as proinflammatory or anti-inflammatory is fraught with a degree of ambiguity. For example, although TNF is a prototypical proinflammatory cytokine, it has well known anti-inflammatory effects, such as inducing apoptosis.2 Likewise, IL-6 has some properties that could be classified as anti-inflammatory. However, it would be an oversimplification to consider it to be an anti-inflammatory cytokine.3 Recent studies have shown that IL-6 is essential for the development of gut barrier dysfunction after hemorrhagic shock and resuscitation in mice,4 and IL-6 may serve as the link between inflammation and thrombosis in sepsis. Isolated human umbilical vein cells treated with IL-6/IL-6 receptor complex produce thrombogenic ultralarge von Willebrand factor fragments and IL-6 also inhibits the cleaving protease, thus further increasing the plasma concentrations of these fragments.5 The release of IL-6 is stimulated by TNF and IL-1 but persists in the plasma for much longer than these other proinflammatory cytokines. As such, IL-6 is a useful marker of proinflammatory cytokine activation. Finally, as shown in Figure 3 of our article,1 both by absolute plasma concentrations of TNF and by the proportion of patients with increased plasma levels, the same pattern we observed with IL-6 is also seen with TNF. Substituting TNF for IL-6 in our analysis does not materially change our results. Thus, we stand by our conclusions that unbalanced activation is uncommon and mortality is highest when both proinflammatory and anti-inflammatory cytokine levels are high.

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview





Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles