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

Abstract

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-gamma 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-gamma-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.

• Authors: 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
• Journal: European journal of immunology (Eur J Immunol) Vol. 33 Issue 10 Pg. 2717-26 (Oct 2003) ISSN: 0014-2980 [Print] Germany
• PMID: 14515255 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Allergens
• Anti-Allergic Agents
• Lipoproteins
• Interleukin-10
• Interleukin-12
• Immunoglobulin E
• Interferon-gamma

Topics

• Allergens (immunology)
• Animals
• Anti-Allergic Agents (pharmacology)
• Eosinophilia (prevention & control)
• Female
• Humans
• Immunoglobulin E (biosynthesis)
• Interferon-gamma (biosynthesis)
• Interleukin-10 (biosynthesis)
• Interleukin-12 (biosynthesis)
• Lipoproteins (pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Schistosoma mansoni (immunology)
• Th2 Cells (drug effects, immunology)