Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated human peripheral blood mononuclear cells.
BACKGROUND
Aluminium hydroxide (alum) is a commonly used adjuvant for specific immunotherapy of allergic diseases. While alum is traditionally associated with murine Th2 sensitization, little is known about its effects on secondary allergic responses in humans.


METHODS
We investigated the in vitro effects of alum on peripheral blood mononuclear cells (PBMC) from atopic donors. PBMC from 18 grass pollen-sensitive rhinitic subjects were stimulated with Phleum pratense (Phl p) in the presence or absence of alum. After 6 days culture, cytokine production was measured by ELISA and T cell proliferation by radiolabelled thymidine incorporation. The effect of alum on the expression of human leucocyte antigen and CD80/CD86 on cultured antigen-presenting cells was assessed by flow cytometry.


RESULTS
PBMC cultured with Phl p and alum showed a significant decrease in both IL-5 and IL-13 production compared with allergen alone (P<0.005 and P<0.001, respectively), but no change in IFN-gamma or IL-12 production or proliferative responses. These alum-induced changes in T helper (Th)2 cytokine production were unaffected by the addition of neutralizing antibodies to IL-4 or IL-12. Culture of PBMC with alum induced increased expression of CD86 (P=0.004) and HLA (P=0.01) on monocytes while the expression of CD80 was decreased (P=0.02).


CONCLUSIONS
Alum down-regulates allergen-driven Th2 cytokine responses while Th1 cytokines are unaffected. These data confirm that alum is a useful adjuvant for inclusion in allergen immunotherapy vaccines.
Wilcock
L K
LK
Upper Respiratory Medicine, Imperial College, National Heart and Lung Institute, London, UK.
Francis
J N
JN
Durham
S R
SR
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000328:Adult; D000485:Allergens / Q000276:immunology*; D000536:Aluminum Hydroxide / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D018793:Interleukin-13 / Q000032:analysis; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D031784:Phleum / Q000276:immunology; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000485:Allergens; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D006680:HLA Antigens; D018793:Interleukin-13; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D018664:Interleukin-12; D015847:Interleukin-4; D000536:Aluminum Hydroxide; D007371:Interferon-gamma