Aluminium hydroxide promotes Th1 responses by peripheral blood-mononuclear cells (PBMCs) obtained from grass pollen-allergic subjects

Abstract

Rationale Grass pollen immunotherapy using an alum-adsorbed vaccine (Alutard SQ, ALK Abello, DENMARK) is effective in severe hayfever (Walker SM et al J Allergy Clin Immunol 2001; etc). In murine studies alum is traditionally regarded as a Th2 adjuvant, whereas there is limited data in humans. We assessed the influence of alum on allergen-stimulated (PBMC) responses in blood from grass pollen-allergic subjects. Methods PBMC from 18 donors were cultured with Phleum pratense with/without alum for 6 days. Cytokine production was analyzed by ELISA. Proliferative responses were analyzed by incorporation of tritiated thymidine. Cell surface markers were measured by flow cytometry. Results PBMC cultured with 50μg/ml of alum and 5μg/ml of allergen displayed a significant decrease in IL-5 production compared with allergen alone (alum + allergen=530pg/ml ± 236, allergen=1024pg/ml ± 274; p=0.001). In addition, alum induced a seven-fold increase in the ratio of IFNγ to IL-5 production (alum + allergen=2.15 ± 1.04, allergen=0.31 ± 0.19; p=0.001) thus favoring a Th1 response. This immune deviation in favor of Th1 responses was not inhibitable by the addition of anti-IL-12 or anti-IL-4 to the culture medium. Alum did not induce IL-12 production nor alter the proliferative response to allergen but did induce a 2-fold increase in IL-10 production in the presence of allergen (alum + allergen=113.1 ± 11.4pg/ml, allergen=67.4 ± 8.8pg/ml; p=0.026). Alum also induced increased expression of CD86 and HLA on monocytes whilst decreasing the expression of CD80. Conclusions In vitro studies of atopic human PBMC responses to grass pollen demonstrate that Alum promotes immune deviation in favor of a Th1 phenotype.