LOCAL TISSUE IRRITATING EFFECTS AND ADJUVANT ACTIVITIES OF CALCIUM-PHOSPHATE AND ALUMINUM HYDROXIDE WITH DIFFERENT PHYSICAL-PROPERTIES

Effects of calcium phosphate and aluminium hydroxide adjuvants with di fferent physical properties were examined in guinea pigs for local his topathological reactions, electron-microscopical changes of macrophage s and adjuvanticity on total IgG antibody response to subcutaneously a dministered ovalbumin (OVA) and tetanus toxoid (TT). Calcium phosphate gel (Ca-gel) induced active inflammatory reactions consisting of neut rophils (pseudoeosinophils) and foamy macrophages associated with many multinuclear giant cells for at least 4 weeks. Aluminium hydroxide ge l (Al-gel) also elicited granulomatous inflammatory reactions consisti ng mainly of macrophages with foamy cytoplasm, small lymphocytes and g iant cells at the injection sites for up to 8 weeks or longer. Severit y of local tissue irritation due to calcium phosphate gel (Ca-gel) was similar to that due to Al-gel except for the duration of the inflamma tory reactions. Calcium phosphate suspension (Ca-sus)-induced local re actions completely ceased by the 4th week, while aluminium hydroxide s uspension (Al-sus)-induced reactions were seen up to the 8th week. Ele ctron-microscopical observations showed that both Al-gel and Al-sus ca used damage of macrophages. The adjuvant activity of Al-gel for OVA or TT was significantly stronger than that of any other adjuvant materia l, whereas those of Ca-gel and Ca-sus were not seen at a dose of 3 mg calcium phosphate per millilitre. Al-sus-TT at a dose of 3 mg aluminiu m hydroxide per millilitre induced very low levels of antibody. These results suggest that calcium phosphate adjuvant may not be an useful a lternative to Al adjuvant. (C) 1997 Elsevier Science Ltd.