Back to Search
Start Over
Effect of oral N-acetyl cysteine supplementation in type 2 diabetic patients on intracellular glutathione content and innate immune responses to Burkholderia pseudomallei
- Source :
- Microbes and Infection. 16:661-671
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Type 2 diabetic patients have increased susceptibility to melioidosis, an infectious disease caused by Burkholderia pseudomallei. We had previously shown that peripheral blood mononuclear cells (PBMCs) from diabetic patients with poor glycemic control had a defective IL-12 and IFNγ response to B. pseudomallei infection, resulting in poor intracellular bacterial control. The impaired IL-12 response was due to glutathione (GSH) deficiency characterized by a low reduced to oxidized glutathione ratio (GSH ratio) and could be restored by the addition of reduced GSH to the infected cells. Our goal is to determine whether N-acetyl cysteine (NAC, a GSH pro-drug) supplementation in diabetic patients could improve their immune control of B. pseudomallei. Type 2 diabetic patients with poor glycemic control were given oral supplementation of NAC for six weeks at 1200 mg daily. Their PBMCs and subsets of immune cells showed a significant increase in free GSH concentration. However, the GSH ratio, IL-12 and IFNγ production, and intracellular bacterial killing upon ex-vivo infection did not improve. Thus, oral NAC supplementation in diabetic patients is sufficient to increase intracellular GSH content in blood cells. However, modulating the free GSH content is not sufficient to improve infection outcome as it is the GSH ratio that regulates the IL-12 response in monocytes.
- Subjects :
- Adult
Male
Burkholderia pseudomallei
Melioidosis
Immunology
Administration, Oral
Type 2 diabetes
Pharmacology
Microbiology
Peripheral blood mononuclear cell
Interferon-gamma
chemistry.chemical_compound
Immune system
medicine
Humans
Cells, Cultured
Aged
Innate immune system
biology
Glutathione
Middle Aged
medicine.disease
biology.organism_classification
Interleukin-12
Immunity, Innate
Acetylcysteine
Infectious Diseases
Diabetes Mellitus, Type 2
chemistry
Female
Intracellular
Subjects
Details
- ISSN :
- 12864579
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Microbes and Infection
- Accession number :
- edsair.doi.dedup.....436fa32ea021fa9ad255efdcfa454e54