Misuse of the C3H/HeJ Mouse in the Determination of Endotoxin Contamination of Various Biologic Preparations

Abstract Much interest was generated when the C3H/HeJ mouse was considered to be refractory to endotoxin, a biologically active product released from Gram-negative bacteria (1, 2). This interest was partly because such a mouse would permit a simple, indirect assay for possible endotoxin contamination in biologic preparations exhibiting the endotoxin-like activity of B cell mitogenesis. For example, if C3H/HeJ splenic B cells with a presumed inability to respond to endotoxin proliferated upon exposure to a certain substance, the mitogenic effect would presumably be due to that substance, not to endotoxin contamination. A precedent for use of the C3H/HeJ mouse in this manner was set with purified protein derivitive (PPD) (1). It was shown that PPD caused proliferation of splenic mouse B cells, including those of the C3H/HeJ to levels equaling that of other mice. Since the C3H/HeJ was considered a low responder to endotoxin, endotoxin contaminants in PPD were excluded as the source of B cell mitogenicity.