Effect of incubation of fresh rabbit serum with a bacterial polysaccharide from S. marcescens on pyrogenicity was examined in normal and tolerant rabbits. In contrast to a number of other reports, no evidence of augmentation of pyrogenicity was obtained; in fact, inhibition of pyrogenicity was frequently seen, particularly in the tolerant animals. Increasing the time of incubation or the amount of serum resulted in further reduction of pyrogenicity. Heating the serum to 68–70°C, but not to 58°C altered this effect on pyrogenic action.

A survey of inbred strains of mice was made to determine whether the phenomenon of dermal hemorrhagic necrosis, as described in rabbits by Shwartzman, could be elicited in mice by bacterial polysaccharide preparations of demonstrated activity in rabbits. The polysaccharide preparations used were obtained from cultures of S. marcescens, S. typhosa, Ps. aeruginosa, and H. pertussis. Ten of the strains tested were unreactive. Three strains of mice and one F1 hybrid subline developed a hemorrhagic lesion at the site of injection of a single, relatively high intradermal dose of polysaccharide. Some increase in incidence of hemorrhagic lesions was obtained when the intradermal dose was followed in 24 hours by an intravenous injection. In the gross and microscopically, the skin lesion produced in mice resembled the Shwartzman reaction in rabbits. An adrenergic blocking agent, SY-28, and an anticoagulant drug, coumadin, both of which block the dermal Shwartzman reaction in rabbits, also blocked the hemorrhagic skin reaction in mice.

Effect of incubation with rabbit serum on the lethality and tumor-necrotizing activity of two pyrogenic polysaccharide preparations was studied in mice carrying i.m. implants of sarcoma 37. The polysaccharide materials were isolated from the same strain of S. marcescens, but were prepared in different laboratories and obtained by different methods. One preparation was a crude, insoluble fraction containing protein, the other was a soluble, trypsin-digested material giving negative protein color tests. Incubation in serum reduced the lethality of the crude preparation by about 50%, but had no effect on the lethality of the more highly purified polysaccharide; it had no demonstrable effect, moreover, on the tumor-necrotizing activity of either preparation. Similar results were obtained with mice rendered tolerant by two injections of polysaccharide in saline. The factor in serum responsible for the decrease in toxicity of the crude preparation was stable to heating at 56°C for 30 minutes, but was inactivated by heating to 70°C for 8 minutes. Tumor implants exhibited apparent refractoriness to the tumor-necrotizing action of the polysaccharide preparations after 6 days growth in hosts rendered tolerant to the lethal action of the material before tumor implantation.