Substitutes for the Mycobacteria in Freund's Adjuvants in the Production of Experimental “Allergic” Encephalomyelitis in the Guinea Pig

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Abstract
Summary: Experimental “allergic” encephalomyelitis (EAE) can be readily induced in guinea pigs by the single intracutaneous injection of neural tissue and Freund's “complete adjuvants” (killed mycobacteria in water-in-oil emulsion). Quantitative comparative studies have revealed that many other acid-fast organisms are equally effective, that Gram-negative organisms are effective but require about ten times as much to produce comparable degrees of EAE, and that Gram-positive organisms are relatively ineffective. Exceptions to this pattern are recognized, but the pattern suggested that organisms rich in capsular lipids and therefore lipophilic were more effective partly because of this surfacetension phenomenon and partly because of the presence of lipopolysaccharide (LPS). Both of these hypotheses were tested, the first by siliconizing ineffective Gram-positive organisms, and the second by testing commercially available LPS from Salmonella typhosa. Although at the moment apparently mutually contradictory since LPS forms an aqueous colloid, the results were according to prediction and indicate that physical as well as chemical aspects of adjuvants must be considered in an attempt to understand the mechanism of action of immunologic adjuvants.

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