Elevated Interleukin-38 Level Associates with Clinical Response to Atorvastatin in Patients with Hyperlipidemia

Cell Physiol Biochem. 2018;49(2):653-661. doi: 10.1159/000493029. Epub 2018 Aug 30.

Abstract

Background/aims: Hyperlipidemia is a risk factor for various cardiovascular and metabolic disorders. And it is tightly related to chronic inflammation. Interleukin-38 (IL-38) represents a new member of anti-inflammatory cytokines. Thus we studied the important role of IL-38 in hyperlipidemia development and treatment.

Methods: The mRNA level of IL-38 in PBMCs (peripheral blood mononuclear cells) and serum IL-38 levels in hyperlipidemia patients and healthy controls were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunoassay (ELISA). The hyperlipidemia patients were further divided into two groups (Sensitive and Resistant Group) according to their clinical response to Atorvastatin therapy. Finally, the effects of IL-38 on hyperlipidemia was evaluated in the mice model.

Results: Data showed that the IL-38 mRNA and serum protein levels were higher in patients with hyperlipidemia compared with healthy controls. And the IL-38 mRNA and serum protein levels were higher in patients sensitive to Atorvastatin therapy than the resistant group. In vitro, IL-38 inhibited the production of IL-6, IL-1β and CRP in PBMCs of patients with hyperlipidemia. In the mice model of hyperlipidemia, IL-38 was also elevated during the hyperlipidemia development. Furthermore, the IL-38 over-expressed by adeno-associated virus significantly inhibited the hyperlipidemia development, inflammatory factor secretion and also the atherosclerosis process.

Conclusion: Thus our data showed that IL-38 might present protective effects on hyperlipidemia treatment.

Keywords: Atherosclerosis; Atorvastatin; Hyperlipidemia; IL-38; Interleukin-38.

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin / pharmacology
  • Atorvastatin / therapeutic use*
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism
  • Cells, Cultured
  • Cholesterol / blood
  • Diet, High-Fat
  • Female
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Humans
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / metabolism
  • Hyperlipidemias / pathology
  • Interleukin-1beta / analysis
  • Interleukin-1beta / metabolism
  • Interleukin-6 / analysis
  • Interleukin-6 / metabolism
  • Interleukins / blood
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged

Substances

  • Anticholesteremic Agents
  • IL-38 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukins
  • C-Reactive Protein
  • Cholesterol
  • Atorvastatin