Granuloma Formation in Normal Guinea Pigs Injected Interadermally With Aluminum and Zirconium Compounds

Abstract

Guinea pigs were injected intradermally with 5 mg, 0.5 mg, and 0.05mg of the following compounds: zirconium carbonate (ZrCO 3 ), aluminum chlorhydrate (ACH), and zirconium aluminum glycine complex (ZAGS), or 6.5 mg, 0.65 mg, and 0.065mg of aluminum hydroxide (Al(OH) 3 ), in 0.1ml of saline. Al(OH) 3 produced measurable granulomas with the 6.5-mg and 0.65-mg doses; those produced by the 6.5-mg dose persisted for over 28 days. No increase in skin thickness was detected with ZrCO 3 . Histologic examination of the Al(OH) 3 granulomas revealed large undifferentiated macrophages and occasional giant cells surrounding the area containing the injected material. There was little evidence of infiltration with other inflammatory cells and no evidence of fibrosis, although there was always some degree of central necrosis. While ZrCO 3 induced no measurable granulomas, the injection site usually contained a small collection of macrophages that had ingested crystalline material. Both ACH and ZAGS produced increases in skin thickness even at the 0.05-mg dos. This began 14 days after injection, and reached a maximum at 21 days. Histologically, the lesions showed granulomas which consisted of shredded bundles of intensely basophilic collagen, which also stained with Weigert's elastic stain. This area contained many giant cells and histiocytes, which were markedly pleomorphic, strongly hyperchromatic, and occasionally phagocytic. This process was succeeded by intense fibrosis. The changes in collagen could be the same as those seen in senile elastosis.