Augmentation of immune response by chicoric acid through the modulation of CD28/CTLA-4 and Th1 pathway in chronically stressed mice

Neuropharmacology. 2011 May;60(6):852-60. doi: 10.1016/j.neuropharm.2011.01.001. Epub 2011 Jan 25.


This study demonstrates the protective effect of chicoric acid (CA) on chronic restraint stress-induced altered T lymphocyte subset distribution and corresponding cytokine secretion patterns in experimental Swiss albino mice. CA has the potential to restore diminished immune response and Th1/Th2 homeostasis in chronically stressed mice as evident by significant increase in lymphocyte proliferation and CD3(+), CD4(+) and CD8(+) T cell population. Interestingly, chicoric acid imparted immunostimulation mainly by upregulating the expression of CD28 and CD80 and downregulating CTLA-4. It exerted stimulatory effect on IL-12, IFN-gamma and IL-2 and suppressed the increased IL-10 levels in chronically stressed mice. It also exhibited a significant lowering effect on raised corticosterone levels and reversed the chronic stress-induced hypertrophy of adrenal glands and atrophy of thymus and spleen, thereby showing its normalizing effect on HPA axis. Our results reveal that CA has the potential to reverse the impact of chronic restraint stress on immune status by normalizing corticosterone levels and augmenting Th1 cytokine profile along with the co-stimulatory molecules particularly CD28/CTLA-4 pathway that plays a very important role in generation of an effective immune response in immune compromised situations.

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / pathology
  • Animals
  • Antigens, CD / metabolism*
  • Atrophy / drug therapy
  • B7-1 Antigen / metabolism
  • CD28 Antigens / metabolism*
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CTLA-4 Antigen
  • Caffeic Acids / pharmacology
  • Caffeic Acids / therapeutic use*
  • Corticosterone / metabolism
  • Hypertrophy / drug therapy
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism
  • Interferon-gamma / metabolism
  • Interleukins / metabolism
  • Lymphocyte Activation / drug effects
  • Mice
  • Spleen / drug effects
  • Spleen / pathology
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / immunology*
  • Succinates / pharmacology
  • Succinates / therapeutic use*
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Thymus Gland / drug effects
  • Thymus Gland / pathology


  • Antigens, CD
  • B7-1 Antigen
  • CD28 Antigens
  • CTLA-4 Antigen
  • Caffeic Acids
  • Ctla4 protein, mouse
  • Inflammation Mediators
  • Interleukins
  • Succinates
  • Interferon-gamma
  • chicoric acid
  • Corticosterone