Monophosphoryl lipid A (MPL) promotes allergen-induced immune deviation in favour of Th1 responses.
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 microg/ml) and MPL (0 and 10 microg/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)-gamma 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-gamma 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.
Puggioni
F
F
Division of Respiratory Medicine, IRCCS Policlinic San Matteo, University of Pavia, Pavia, Italy.
Durham
S R
SR
Francis
J N
JN
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000485:Allergens / Q000276:immunology*; D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006109:Poaceae / Q000276:immunology; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000473:pathology*
D000276:Adjuvants, Immunologic; D000485:Allergens; D000906:Antibodies; D016207:Cytokines; D008050:Lipid A; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; C048436:monophosphoryl lipid A