Immunomodulatory effects of aqueous birch pollen extracts and phytoprostanes on primary immune responses in vivo

J Allergy Clin Immunol. 2007 Aug;120(2):293-9. doi: 10.1016/j.jaci.2007.03.017. Epub 2007 Apr 23.


Background: We recently demonstrated that pollen not only function as allergen carriers but also as rich sources of bioactive lipids, such as phytoprostanes, that modulate human dendritic cell (DC) function in a way that results in an enhanced T(H)2 polarization in vitro.

Objective: Here we analyzed the immunomodulatory capacities of Betula alba (white birch) aqueous pollen extracts (Bet-APEs) and pollen-associated phytoprostanes in the murine system in vitro and in vivo.

Methods: DC function was analyzed in vitro by using BALB/c bone marrow-derived DCs. T-cell responses were analyzed with DO11.10 peptide 323-339 from chicken ovalbumin (OVA)-specific CD4 T cells as responder cells. For in vivo studies, OVA-specific CD4 T cells were adoptively transferred into BALB/c mice. Twenty-four hours later, mice were challenged by means of intranasal application of OVA in the absence or presence of Bet-APEs or phytoprostanes. Polarization of T-cell responses in vivo was analyzed in draining lymph node cells.

Results: In vitro Bet-APEs and E(1)-phytoprostanes dose-dependently inhibited LPS-induced IL-12p70 of DCs. In addition, Bet-APEs induced a T(H)2 polarization in vitro. Similarly, intranasal instillation of Bet-APEs in vivo, together with the antigen, lead to increased IL-4, IL-5, and IL-13 secretion and decreased IFN-gamma secretion from antigen-specific T cells in the draining lymph nodes. In contrast, intranasal E1- and F1-phytoprostanes downregulated both T(H)1 and T(H)2 cytokine production in vivo.

Conclusion: Pollen release water-soluble factors that display T(H)2-polarizing capacities in vivo independently of E(1)- and F(1)-phytoprostanes.

Clinical implications: Identification of the underlying mechanisms might open new approaches for pharmacologic intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibody Formation / drug effects*
  • Betula / chemistry*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chickens
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Dose-Response Relationship, Drug
  • Epitopes
  • Immunologic Factors
  • Interleukin-12 / antagonists & inhibitors
  • Interleukin-12 / biosynthesis
  • Isoprostanes / administration & dosage
  • Isoprostanes / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Lymph Nodes / cytology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Pollen / chemistry*
  • Solutions
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Helper-Inducer / cytology
  • Th1 Cells / cytology
  • Th2 Cells / cytology


  • Cytokines
  • Epitopes
  • Immunologic Factors
  • Isoprostanes
  • Lipopolysaccharides
  • Plant Extracts
  • Solutions
  • Interleukin-12
  • Ovalbumin