Immunoadjuvanticity of Endotoxins and Nontoxic Derivatives for Normal and Leukemic Immunocytes

Endotoxins from many Gram negative bacteria are known to be immunostimulators. For example, administration of crude or even purified lipopolysaccharide (LPS) endotoxin preparations into experimental animals challenged with various soluble and/or particulate antigens may result in altered immune responses, including enhanced responses, especially when the endotoxins are given shortly before or simultaneously with antigen (4, 10, 14, 15, 17, 19, 24, 25, 26). Studies in these laboratories have shown that a polysaccharide (PS)-rich derivative from endotoxins lacking the lipid A moiety and free of toxicity is a potent immunostimulant for normal mice (7, 8, 11). For example, the PS obtained from Serratia marcescens is equivalent to the intact endotoxin in enhancing the antibody response to a T cell dependent antigen such as sheep erythrocytes (SRBC) in vitro. In vivo the PS was less effective than LPS in enhancing the immune response to SRBC but still considerable adjuvant effect could be demonstrated (1, 2). Injection of SRBC into normal mice or addition of this antigen to cultures of splenocytes from non-immunized mice results in an antibody response readily detected by the hemolytic plaque assay in vitro. Furthermore, treatment of the animals or cell cultures with either LPS or its PS derivative results in enhanced antibody formation.