Amyloid resorption: possible role of multinucleated giant cells; the apparent failure of penicillamine treatment

An attempt was made to explore methods of therapy for amyloidosis. Penicillamine was selected since it has been found to interfere with the immune response. Recent studies have emphasized the immunologic nature of amyloid. Amyloid was induced in rabbits with sodium caseinate. D Penicillamine alone, and with casein were given to other rabbits. Studies were made referable to serum protein, sialic acid and fibrinogen concentrations. Pathologic studies, including both light and electron microscopy, were made on the spleen, liver and kidney. Following 15 to 27 weeks of sodium caseinate, 10 of 19 rabbits had extensive splenic amyloidosis. After 38 to 53 weeks of casein treatment over half of the rabbits had minimal splenic amyloidosis (1+), trace deposits, or no evidence of splenic amyloidosis at all. Spontaneous resorption of splenic amyloid occurred. D Penicillamine did not alter the pattern of splenic amyloid accumulation or apparent regression. A histologic finding of particular interest in the spleen was the presence of giant cells containing what appeared to represent cytoplasmic amyloid, suggesting phagocytic activity. These cells were not present in the liver and kidney. Other giant cells were also present but did not have material suggestive of amyloid. The presence of these giant cells in the spleen suggest the possibility that amyloid resorption is accomplished by active phagocytosis. These giant cells appear to originate within the Billroth cords and some seem to arise from sinusoidal lining cells. The authors suggest that this study has important clinical and biologic implications. From the cinical point of view, identification of a mechanism of amyloid resorption may lead to the development of new approaches to therapy. From the biologic point of view the reticuloendothelial cell which is generally implicated in amyloid formation, and the giant cell, which may play a role in its resorption, are both thought to be derived from the same primordial mesenchymal cell. A subtle balance of forces upon this cell may, at one time, stimulate it to produce amyloid and under other conditions prompt it to engulf and digest amyloid. (Rigdon - Galveston, Tex.)