Inhibition of T helper 2-type responses, IgE production and eosinophilia by synthetic lipopeptides

Cezmi A. Akdis, Fatimah Kussebi, Bali Pulendran, Mübeccel Akdis, Roger P. Lauener, Carsten B. Schmidt-Weber, Sven Klunker, Gülbu Isitmangil, Natasha Hansjee, Thomas A. Wynn, Stephanie Dillon, Peter Erb, Gerhard Baschang, Kurt Blaser, Sefik S. Alkan

Research output: Contribution to journalReview articlepeer-review

105 Scopus citations


In allergy and asthma, the fine balance between the T helper (Th) 1, Th2 and T regulatory cytokine responses appears to be shifted towards Th2. Here, we report that synthetic lipopeptides which contain the typical lipid part of the lipoprotein of gram-negative bacteria stimulate a distinct regulatory cytokine pattern and inhibit several Th2 cell-related phenomena. The most potent analogue of synthetic lipopeptides, lipopeptide CGP 40774 (LP40) was not active in MyD88-deficient mice and stimulated Toll-like receptor (TLR)-2, but not TLR-4. LP40 potentiated the production of IFN-γ and IL-10, but not IL-4 and IL-5 by human T cells. In addition, triggering of TLR-2 by lipopeptides promoted the in vitro differentiation of naive T cells towards IL-10- and IFN-γ-producing T cells and suppressed IL-4 production by Th2 cells. Accordingly, LP40 inhibited IgE production induced by allergen, anti-IgD antibody, Nippostrongylus brasiliensis or murine acquired immunodeficiency virus. Furthermore, ovalbumin-induced lung eosinophilic inflammation was abolished and Schistosoma mansoni egg-induced granuloma size and eosinophil counts were suppressed in mice by LP40. These results demonstrate that stimulation of TLR-2 by lipopeptides represents a novel way for possible treatment of allergy and asthma by regulating the disrupted cytokine balance.

Original languageEnglish
Pages (from-to)2717-2726
Number of pages10
JournalEuropean Journal of Immunology
Issue number10
StatePublished - Oct 2003
Externally publishedYes


  • Allergy
  • IgE
  • Lipopeptide
  • T cells
  • Toll-like receptor 2


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