Propentofylline, phosphodiesterase and adenosine reuptake inhibitor modulates lymphocyte subsets and lymphocyte activity after in-vivo administration in non-immunized and SRBC-immunized mice

J Pharm Pharmacol. 2017 Sep;69(9):1166-1177. doi: 10.1111/jphp.12760. Epub 2017 Jun 16.

Abstract

Objectives: The aim of the study was to investigate immunomodulatory effect of in-vivo administered propentofylline on the subsets and activity of murine lymphocytes.

Methods: Propentofylline (3 mg/kg) was administered orally to 8-week-old Balb/c mice, once or six times at 12-h intervals. The lymphocyte subsets, regulatory T cells, IL-5 and TNF levels were determined 12 h and 24 h after a single dose or after the sixth dose of the drug in non-immunized mice. Humoral immune response in sheep red blood cells (SRBC)-immunized mice was determined 4, 7 and 14 days after immunization.

Key findings: Propentofylline inhibited thymocyte maturation (increase in CD4- CD8- thymocyte subset and decrease in the percentage of CD4+ CD8+ thymocytes) and modulated the lymphocyte subsets in spleen and mesenteric lymph nodes. An increase in the absolute count and percentage of splenic regulatory T cells (CD4+ CD25+ Foxp3+ cells) was noticed 24 h after single administration of the drug. Propentofylline lowered serum level of IL-5 and did not affect TNF concentration. Only a weak inhibitory effect on anti-SRBC humoral immune response was observed.

Conclusions: Propentofylline administration induced inhibition of thymocyte maturation and an increase in Treg subset that might be beneficial for an inhibition of immune response.

Keywords: cytokines; lymphocyte subsets; mice; propentofylline; regulatory T cells.

MeSH terms

  • Adenosine / metabolism
  • Animals
  • Erythrocytes / immunology
  • Female
  • Immunity, Humoral / drug effects*
  • Interleukin-5 / blood
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymphocyte Subsets / drug effects*
  • Lymphocyte Subsets / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neuroprotective Agents / pharmacology*
  • Phosphodiesterase Inhibitors / pharmacology
  • Sheep
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Thymocytes / immunology
  • Time Factors
  • Xanthines / pharmacology*

Substances

  • Interleukin-5
  • Neuroprotective Agents
  • Phosphodiesterase Inhibitors
  • Xanthines
  • propentofylline
  • Adenosine