Clinical Investigations

Innate Immune Functions of Immature Neutrophils in Patients With Sepsis and Severe Systemic Inflammatory Response Syndrome*

Drifte, Geneviève MD^1,2; Dunn-Siegrist, Irène Msc^1,2; Tissières, Pierre MD, PhD^1,2; Pugin, Jérôme MD^1,2

¹ Laboratory of Intensive Care, University Hospitals of Geneva, University of Geneva, Switzerland.

² Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Switzerland.

* See also p. 925.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (http://journals.lww.com/ccmjournal).

This study was supported, in part, by grants (320080-122034 and 310030-141143 to Dr. Pugin) from the Swiss National Foundation for Scientific Research. Dr. Drifte was supported by the Swiss National MD-PhD program (323500-128875) and a grant from the Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital of Geneva, Switzerland.

The authors have not disclosed any potential conflicts of interest.

Address requests for reprints to: Jérôme Pugin, MD, Hôpitaux Universitaires de Genève, Soins Intensifs–Site E, 4, rue Gabrielle-Perret-Gentil, CH-1211, Genève 14, Switzerland, E-mail: [email protected]

Critical Care Medicine 41(3):p 820-832, March 2013. | DOI: 10.1097/CCM.0b013e318274647d

Abstract

Objective:

A hallmark of sepsis and severe systemic inflammatory response syndrome (SIRS) is the massive recruitment of immature neutrophils from the bone marrow into the circulation (left shift, band forms). Their capacity to participate in innate defense against bacteria is ill defined. We aimed at comparing various innate immune functions of mature vs. immature neutrophils circulating during sepsis and SIRS.

Design:

Prospective, observational cohort study.

Setting:

Tertiary level ICU and associated research laboratory.

Patients:

Thirty-three ICU patients with sepsis; 12 ICUs with SIRS; 32 healthy volunteers.

Interventions:

Twenty milliliters of whole heparinized blood was used for in vitro studies including neutrophil viability and apoptosis, surface expression of CD16, Toll-like receptors (1) 4 and TLR2, CD14, MD-2, HLA-DP,-DQ and -DR, and CXCR2, chemotaxis, phagocytosis, bacterial killing, and tumor necrosis factor-α/interleukin-10 baseline intracellular cytokine levels.

Measurements and Main Results:

Immature neutrophils were capable of mediating important innate immune functions such as bacterial phagocytosis and killing via the production of reactive oxygen species, although less efficiently than mature neutrophils. Immature neutrophils had a longer life span and resistance to spontaneous apoptosis, and could mature ex vivo. They expressed lower levels of receptors for bacterial molecules such as CD14 and MD-2 and migrated less efficiently than mature granulocytes. Immature neutrophils had higher basal intracellular tumor necrosis factor-α/interleukin-10 ratio than that of mature neutrophils, suggesting a proinflammatory phenotype. No significant differences were observed between immature neutrophils isolated from patients with sepsis and those from patients with severe SIRS.

Conclusions:

Despite their “immaturity”, band forms are capable of mediating crucial innate immune functions during severe infections and sepsis. Their fate and capacity to mature in vivo remain to be determined.