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Mary White, MD, MSc, FFCAI; Arun Mankan, MD; Matthew W. Lawless, BSc, PhD; Michael J. O’Dwyer, MD, FFCAI; Ross McManus, BSc, PhD; Thomas Ryan, MD, FFCAI

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In the interesting article by Kellum et al¹ on the systemic cytokine response to pneumonia in a cohort study of 1886 subjects hospitalized for community-acquired pneumonia (CAP), the authors report that the highest risk of death was with combined high levels of the proinflammatory cytokine interleukin (IL)-6 and the anti-inflammatory cytokine IL-10. They conclude that mortality is highest when both anti-inflammatory and proinflammatory cytokine levels are high.

Although IL-6 is frequently generated with the other proinflammatory cytokines tumor necrosis factor (TNF-) and IL-1, it is unclear whether its precise actions are predominantly proinflammatory or anti-inflammatory. In an IL-6 animal knockout model, endotoxic lung or lipopolysaccharide (LPS)-induced acute inflammation induces higher levels of TNF- and interferon (IFN-) in IL-6^–/– than in IL-6^+/+ mice. . . . [Full Text of this Article]

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RELATED ARTICLE

Understanding the Inflammatory Cytokine Response in Pneumonia and Sepsis: Results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study
John A. Kellum, Lan Kong, Mitchell P. Fink, Lisa A. Weissfeld, Donald M. Yealy, Michael R. Pinsky, Jonathan Fine, Alexander Krichevsky, Russell L. Delude, Derek C. Angus, and for the GenIMS Investigators
Arch Intern Med. 2007;167(15):1655-1663.
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RELATED LETTER

Mortality in Humans With Pneumonia and Sepsis Is Related to an Uncompensated Anti-inflammatory Response to Infection—Reply
John A. Kellum and Derek C. Angus
Arch Intern Med. 2008;168(13):1469.
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