Impaired Inflammatory Response to LPS in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a severe health problem worldwide, reaching epidemic levels. High susceptibility to infections of T2DM patients indicates dysregulated immune responses to pathogens. However, innate immune responses, including monocyte functions, in T2DM are poorly investigated. Therefore, in this study we aimed to assess lipopolysaccharide- (LPS-) induced immune responses of circulating monocytes from T2DM patients. The results showed that monocytes from T2DM were hyporesponsive to LPS challenge as reflected by significantly suppressed secretion of TNFα (p < 0.01) and expression of CD11b (p < 0.001) and TLR4 (p < 0.001) compared to those in monocytes from healthy subjects. Furthermore, LPS-induced IL-10 levels were similar in diabetic and healthy supernatants, while expression levels of CD163 were found to be downregulated on monocytes from T2DM (p < 0.001) suggesting impaired ability of monocytes to switch their phenotype to anti-inflammatory. Taken together, our results suggest compromised function of monocytes in T2DM, which may explain, at least partly, high incidence of infection in these patients.

• Publication year

  2018

• Venue

  International Journal of Inflammation

• Publication date

  2018-01-14

• Fields of study

  Medicine

• Identifiers
  DOI 10.1155/2018/2157434PMID 29568481PMCID 5820544
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• The results support compromised monocyte function in type 2 diabetes mellitus and suggest it may partly explain the high infection incidence in these patients.

  Confidence 0.90

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• CD163 expression is downregulated on monocytes from type 2 diabetes mellitus after LPS challenge, indicating impaired switching toward an anti-inflammatory phenotype.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• LPS-induced IL-10 levels are similar in diabetic and healthy monocyte supernatants.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• Circulating monocytes from patients with type 2 diabetes mellitus show reduced responsiveness to lipopolysaccharide, with lower TNFα secretion and lower CD11b and TLR4 expression than monocytes from healthy subjects.

  Confidence 0.99

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review

• anti-inflammatory phenotype

  phenotype

  A monocyte activation state associated with regulatory, less inflammatory behavior.

  Aliases: alternative activation state

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• cd11b

  cell surface marker, integrin

  A monocyte surface integrin marker assessed as part of the activation response.

  Aliases: ITGAM

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• cd163

  cell surface marker, scavenger receptor

  A monocyte surface scavenger receptor associated with anti-inflammatory polarization.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• circulating monocytes

  cell type

  Peripheral blood monocytes isolated from the bloodstream for ex vivo stimulation assays.

  Aliases: blood monocytes, monocytes from peripheral blood

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• il-10

  cytokine

  An anti-inflammatory cytokine measured in the supernatants after lipopolysaccharide challenge.

  Aliases: interleukin-10

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• infection incidence

  outcome

  The frequency of infections in the patient population discussed in the abstract.

  Aliases: high incidence of infection

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• lipopolysaccharide (lps)

  stimulus, molecule

  A bacterial endotoxin used here as the inflammatory stimulus applied to monocytes.

  Aliases: LPS, lipopolysaccharide

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• tlr4

  receptor

  A Toll-like receptor on monocytes that recognizes lipopolysaccharide.

  Aliases: Toll-like receptor 4

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• tnfα

  cytokine

  A pro-inflammatory cytokine measured in monocyte supernatants after stimulation.

  Aliases: TNF-alpha, TNF-α

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review
• type 2 diabetes mellitus

  condition

  A chronic metabolic disorder characterized by insulin resistance and hyperglycemia, used here as the patient group under investigation.

  Aliases: T2DM, type 2 diabetes

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) review

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