Effects of thymol and carvacrol on T-helper cell subset cytokines and their main transcription factors in ovalbumin-immunized mice

J Immunotoxicol. 2016 Sep;13(5):729-37. doi: 10.3109/1547691X.2016.1173134. Epub 2016 Jul 14.

Abstract

Thymol and carvacrol, two main components of thyme, have several valuable effects on the immune system. This study aims to evaluate the effects of these components on T-helper (TH) cell responses and their subsets in mice immunized with ovalbumin. The effects of these components on: a specific in vivo immune response were evaluated by assessing changes in delayed-type hypersensitivity (DTH); ex vivo splenocyte proliferative responses were evaluated using a BrdU assay gene expression of cytokines and key transcription factors involved in T-cells subset differentiation among the mouse splenocytes were assessed using real-time polymerase chain reaction (PCR); and splenocyte cytokine formation (ex vivo) and levels of the cytokines in mouse sera were measured by ELISA. Mice treated with thymol or carvacrol had reduced DTH responses (26% and 50%, respectively) compared with control mice. Thymol and carvacrol each diminished splenocyte proliferation to nearly 65-72% of control levels (p < 0.01). These agents also led to decreased TH1 [interleukin (IL)-2, interferon (IFN)-γ)], TH2 (IL-4) and TH17 (IL-17A) levels in the splenocyte cultures and in the sera of mice but increased levels of IL-10 and transforming growth factor (TGF)-β. Treated immunized mice showed significantly reduced T-box 21 (T-bet) expression from 3.8 [± 0.3]-fold in untreated ovalbumin-immunized mice to 0.9 [± 0.4]-(thymol) and 0.8 [± 0.2]-fold (carvacrol) (p < 0.01). GATA binding protein 3 (GATA-3) expression declined from 3.4 [± 0.4]- to 0.5 [± 0.3]-fold (thymol) and 0.6 [± 0.4]-fold (carvacrol), whereas RORγc decreased from 13.4 [± 1.6]- to 1.5 [± 0.6]-fold (thymol) and 0.8 [± 0.4]-fold (carvacrol) (p < 0.001). As carvacrol and thymol each suppressed the antigen-specific immune response by reducing TH cell-related cytokines\specific transcription factors, this indicated their potential to modulate destructive immune responses attributed to T-cells over-activation.

Keywords: Carvacrol; T-helper cells; immunization; immunomodulation; ovalbumin; thymol.

MeSH terms

  • Animals
  • Antigens / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Cymenes
  • Cytokines / metabolism
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism
  • Hypersensitivity, Delayed / drug therapy*
  • Hypersensitivity, Delayed / immunology
  • Immunization
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Monoterpenes / therapeutic use*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Ovalbumin / immunology
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / immunology
  • Thymol / therapeutic use*
  • Thymus Plant / immunology*
  • Transcriptional Activation

Substances

  • Antigens
  • Cymenes
  • Cytokines
  • GATA3 Transcription Factor
  • Monoterpenes
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Thymol
  • Ovalbumin
  • carvacrol