Aluminum as an adjuvant in Crohn’s disease induction

Abstract

Alum (AlK(SO4)2) is an adjuvant commonly utilized in vaccines, and is a ubiquitous element used extensively in contemporary life. Food, air, water, waste, the earth’s surface, and pharmaceuticals all represent pathways of aluminum (Al) exposure. Crohn's disease (CD) is a chronic relapsing intestinal inflammation in genetically susceptible individuals and is caused by yet unidentified environmental factors. Al is a potential factor for the induction of inflammation in CD, and its immune activities share many characteristics with the immune pathology of CD: many luminal bacterial or dietary compounds can be adsorbed to the metal surface and induce Th1 profile cytokines, shared cytokines/chemokines, co-stimulatory molecules, and intracellular pathways and stress-related molecular expression enhancement, affecting intestinal macrobiota, trans-mural granuloma formation, and colitis induction in an animal CD model. The inflammasome plays a central role in Al mode of action and in CD pathophysiology. It is suggested that Al adjuvant activity can fit between the aberrations of innate and adaptive immune responses occurring in CD. The CD mucosa is confronted with numerous inappropriate bacterial components adsorbed on the Al compound surface, constituting a pro-inflammatory supra-adjuvant. Al fits the diagnostic criteria of the newly described autoimmune/inflammatory syndrome induced by adjuvants. If a cause and effect relationship can be established, the consequences will greatly impact public health and CD prevention and management.