Interleukin-6 delays neutrophil apoptosis

W. L. Biffl, E. E. Moore, F. A. Moore, C. C. Barnett Jr, V. S. Carl and V. N. Peterson
Department of Surgery, Denver General Hospital, USA.

BACKGROUND: Neutrophil (PMN) apoptosis promotes the phagocytosis of PMNs without inciting an inflammatory response or local cytotoxic effect. This is important in the normal resolution of inflammatory processes and the control of tissue injury. Conversely, a delay in PMN apoptosis may facilitate PMN-mediated organ dysfunction by extending PMN functional integrity at an inflammatory site. Elevated circulating and tissue levels of interleukin-6 (IL-6) have been associated with postinjury organ dysfunction, and IL-6 appears to augment PMN cytotoxic functions. Therefore, we hypothesized that IL-6 delays PMN apoptosis, thereby enhancing PMN-mediated cytotoxicity. METHODS: Neutrophils isolated from healthy human donors were incubated for 24 hours in enriched RPMI 1640 cell culture medium at 37 degrees C in 5% carbon dioxide. Subgroups were incubated with IL-6, heat-denatured IL-6, or buffer alone. Apoptosis was assessed morphologically using acridine orange-ethidium bromide stain, and biochemically by DNA gel electrophoresis. Functional capacity of PMNs was assessed by superoxide generation after activation with phorbol myristate acetate or platelet-activating factor plus formyl-methionyl-leucyl-phenylalanine. RESULTS: Treatment with IL-6 resulted in a greater population of surviving (nonapopototic) PMNs after 24 hours. In addition, the IL-6-treated population produced more superoxide after 24 hours than did the untreated or heat-denature IL-6-treated groups, after either activating stimulus. CONCLUSIONS: Interleukin-6 delays PMN apoptosis, resulting in a larger population of surviving PMNs with a greater collective capacity for superoxide production. This could potentially facilitate PMN-mediated tissue injury and may be a mechanism whereby IL-6 contributes to organ dysfunction.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The role and regulation of apoptosis in sepsis
Wesche-Soldato et al.
Innate Immunity 2005;11:375-382.
ABSTRACT  

Apoptosis of Circulating Neutrophils in COPD Patients
Pletz et al.
Chest 2005;127:1464-1465.
FULL TEXT  

In Vivo Interleukin-6 Protects Neutrophils from Apoptosis in Osteomyelitis
Asensi et al.
Infect. Immun. 2004;72:3823-3828.
ABSTRACT | FULL TEXT  

Decreased neutrophil apoptosis in tracheal fluids of preterm infants at risk of chronic lung disease
Oei et al.
Arch. Dis. Child. Fetal Neonatal Ed. 2003;88:F245-F249.
ABSTRACT | FULL TEXT  

Cross-talk between tumor cells and neutrophils through the Fas (APO-1, CD95)/FasL system: human glioma cells enhance cell viability and stimulate cytokine production in neutrophils
Hor et al.
J. Leukoc. Biol. 2003;73:363-368.
ABSTRACT | FULL TEXT  

Neutrophil-Related Inflammatory Mediators in Septic Acute Respiratory Distress Syndrome
Kinoshita et al.
J Intensive Care Med 2002;17:308-316.
ABSTRACT  

Ketamine Attenuates Neutrophil Activation After Cardiopulmonary Bypass
Zilberstein et al.
Anesth. Analg. 2002;95:531-536.
ABSTRACT | FULL TEXT  

Differential regulation of spontaneous and immune complex-induced neutrophil apoptosis by proinflammatory cytokines. Role of oxidants, Bax and caspase-3
Ottonello et al.
J. Leukoc. Biol. 2002;72:125-132.
ABSTRACT | FULL TEXT  

Circulating Mediators and Organ Function in Patients Undergoing Planned Relaparotomy vs Conventional Surgical Therapy in Severe Secondary Peritonitis
Zugel et al.
Arch Surg 2002;137:590-599.
ABSTRACT | FULL TEXT  

Inhibition of neutrophil apoptosis after coronary bypass operation with cardiopulmonary bypass
Chello et al.
Ann. Thorac. Surg. 2002;73:123-129.
ABSTRACT | FULL TEXT  

Autoreactivity Against Interleukin 6 as a Risk Factor in Elderly Patients With Colorectal Carcinoma
Wakuda et al.
Arch Surg 2001;136:1274-1279.
ABSTRACT | FULL TEXT  

The Effects of Glucocorticoid Therapy on Inflammatory Responses to Coronary Artery Bypass Graft Surgery
Rumalla et al.
Arch Surg 2001;136:1039-1044.
ABSTRACT | FULL TEXT  

Apoptosis in sepsis: a new target for therapeutic exploration
OBERHOLZER et al.
FASEB J. 2001;15:879-892.
ABSTRACT | FULL TEXT  

Apoptosis and Surgical Trauma: Dysregulated Expression of Death and Survival Factors on Peripheral Lymphocytes
Delogu et al.
Arch Surg 2000;135:1141-1147.
ABSTRACT | FULL TEXT  

Biphasic Ocular Inflammatory Response to Endotoxin-Induced Uveitis in the Mouse
Shen et al.
Arch Ophthalmol 2000;118:521-527.
ABSTRACT | FULL TEXT  

Spontaneous Skin Ulceration and Defective T Cell Function in CD18 Null Mice
Scharffetter-Kochanek et al.
JEM 1998;188:119-131.
ABSTRACT | FULL TEXT  

Interleukin-6 Production by Human Neutrophils After Fc-Receptor Cross-Linking or Exposure to Granulocyte Colony-Stimulating Factor
Ericson et al.
Blood 1998;91:2099-2107.
ABSTRACT | FULL TEXT  

Neutrophil apoptosis in the acute respiratory distress syndrome
Matute-Bello et al.
Am. J. Respir. Crit. Care Med. 1997;156:1969-1977.
ABSTRACT | FULL TEXT