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

• Published in: European journal of immunology 2003-10, Vol.33 (10), p.2717-2726
• Main Authors: Akdis, Cezmi A., Kussebi, Fatimah, Pulendran, Bali, Akdis, Mübeccel, Lauener, Roger P., Schmidt‐Weber, Carsten B., Klunker, Sven, Isitmangil, Gülbu, Hansjee, Natasha, Wynn, Thomas A., Dillon, Stephanie, Erb, Peter, Baschang, Gerhard, Blaser, Kurt, Alkan, Sefik S.
• Format: Article
• Language: English
• Subjects: Allergens - immunology; Allergy; Animals; Anti-Allergic Agents - pharmacology; Eosinophilia - prevention & control; Female; Humans; IgE; Immunoglobulin E - biosynthesis; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Interleukin-12 - biosynthesis; Lipopeptide; lipopeptides; Lipoproteins - pharmacology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; MyD88 protein; Nippostrongylus brasiliensis; Schistosoma mansoni; Schistosoma mansoni - immunology; Th2 Cells - drug effects; Th2 Cells - immunology; Tlr2 protein; Toll‐like receptor 2; T cells
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200323329

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.