Korean J Pediatr.  2008 Oct;51(10):1096-1101. 10.3345/kjp.2008.51.10.1096.

TNF-alpha stimulated IL-8 and IL-10 expression in monocytes from patients with chronic granulomatous disease

• Shin KS

• KMID: 2280318
• DOI: http://doi.org/10.3345/kjp.2008.51.10.1096

Abstract

PURPOSE: Patients with chronic granulomatous disease (CGD) have genetic mutations in a component of the NADPH oxidase enzyme that is necessary for the generation of the superoxide anion. The profound defect in innate immunity is reflected by the patients susceptibility to catalase-positive bacteria and fungi. In addition, CGD patients display signs of persistent inflammation, which is not associated only with deficient superoxide anion production. The aim of this study was to elucidate the cytokine responses in CGD patients after TNF-alpha stimulation.
METHODS
Heparinized blood samples were collected from 8 CGD patients and 10 healthy volunteers. Monocytes (1x10(6) cell/well) isolated by the magnet cell isolation system were incubated with a constant amount of TNF-alpha (10 ng/mL) at 37degrees C for 6 h. Incubated cells were harvested at 60-min intervals for IL-8 and IL-10 mRNA analysis, and the supernatant was collected at the same intervals to determine IL-8 and IL-10 expression. Monocytes from healthy volunteers were also incubated with antioxidants followed by TNF-alpha stimulation for IL-8 and IL-10 expression.
RESULTS
In CGD patients, a high expression of IL-8 together with a significantly higher IL-10 expression than in the healthy controls was seen after TNF-alpha stimulation. Moreover, normal monocytes treated with antioxidants exhibited increased IL-8 responses.
CONCLUSION
The absence of phagocyte-derived reactive oxidants in CGD might be associated with a dysregulated production of pro- and antiinflammatory cytokines. Additional research related to reactive oxidants is needed to clarify the role of cytokines in CGD patients.

Keyword

Chronic granulomatous disease; Nicotinamide adenine dinucleotide phosphate oxidase; Monocyte; Tumor necrosis factor-alpha; Interleukin-8; Interleukin-10; Persistent inflammation; Reactive oxidants

MeSH Terms

Antioxidants
Bacteria
Cell Separation
Cytokines
Fungi
Granulomatous Disease, Chronic
Heparin
Humans
Immunity, Innate
Inflammation
Interleukin-10
Interleukin-8
Magnets
Monocytes
NADPH Oxidase
Oxidants
RNA, Messenger
Superoxides
Tumor Necrosis Factor-alpha
Antioxidants
Cytokines
Heparin
Interleukin-10
Interleukin-8
NADPH Oxidase
Oxidants
RNA, Messenger
Superoxides
Tumor Necrosis Factor-alpha