Monophosphoryl lipid A (MPL®) promotes allergen‐induced immune deviation in favour of Th1 responses

• Published in: Allergy (Copenhagen) Vol. 60; no. 5; pp. 678 - 684
• Main Authors: Puggioni, F., Durham, S. R., Francis, J. N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Munksgaard International Publishers 01.05.2005; Blackwell; Blackwell Publishing Ltd
• Subjects: adjuvants; Adjuvants, Immunologic - pharmacology; Adult; Allergens - immunology; Allergic diseases; Allergies; allergy; Antibodies - pharmacology; Biological and medical sciences; Cell Division - drug effects; Cells, Cultured; Cytokines - biosynthesis; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; human; Humans; Immune system; Immunopathology; Intercellular Adhesion Molecule-1 - metabolism; Interleukin-12 - biosynthesis; Interleukin-12 - immunology; Lipid A - analogs & derivatives; Lipid A - pharmacology; Lipids; Male; Medical sciences; Medical treatment; Monocytes - immunology; Monocytes - metabolism; Monocytes - pathology; Phleum pratense; Poaceae - immunology; Pollen; Pollen - immunology; Rhinitis, Allergic, Seasonal - blood; Rhinitis, Allergic, Seasonal - immunology; Rhinitis, Allergic, Seasonal - metabolism; Salmonella minnesota; Th1 Cells - pathology; Th1/2 cytokines; T‐lymphocytes; Human; Immunopathology; Allergy; Thl/2 cytokines; Cytokine; Th1 lymphocyte; Lipids; adjuvants; allergy; human; T-lymphocytes; Growth factor receptor; Immunology; Mpl ligand; T-Lymphocyte; Adjuvant; Immune deviation; Allergen
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.2005.00762.x

Background:  Monophosphoryl lipid A (MPL®) is a nontoxic derivative of the lipopolysaccharide (LPS) of Salmonella minnesota R595. MPL has been used as an adjuvant in grass and tree pollen vaccines for the treatment of seasonal allergic rhinitis. Little is known about the influence of MPL on cellular responses to allergens in man. We therefore studied the effects of MPL in vitro on peripheral blood mononuclear cells (PBMC) obtained from patients with grass pollen hay fever. Methods:  The PBMCs from 13 subjects were cultured with grass pollen Phleum pratense extract (0, 2 and 20 μg/ml) and MPL (0 and 10 μg/ml; defined as an optimal concentration in preliminary studies) and after 6 days proliferative responses were measured by thymidine incorporation and cytokine production by enzyme‐linked immunosorbent assay (ELISA). Results:  Proliferative responses were unaffected by the presence of MPL whereas MPL induced a significant increase in allergen‐induced interferon (IFN)‐γ production [allergen alone, 645 ± 466 pg/ml (mean ± SE) vs allergen + MPL, 3232 ± 818 pg/ml; P < 0.001]. In addition, there was a significant decrease in interleukin (IL)‐5 production (4307 ± 1030 pg/ml vs 2997 ± 826 pg/ml; P < 0.01). Although MPL alone could induce modest increases in IL‐10 production, MPL did not influence the production of this cytokine in allergen‐stimulated cultures. Addition of neutralizing antibody against IL‐12 resulted in 95% inhibition of MPL‐induced IFN‐γ production. Depletion of monocytes from the culture system abrogated the effects of MPL on elevated cytokine production. Conclusions:  In summary, use of MPL with grass pollen extract results in immune deviation of allergen‐induced peripheral Th2‐cell responses in favour of ‘protective’ Th1 responses in an IL‐12 and monocyte‐dependent fashion.