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Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
Comparison of endotoxins and cutaneous burn toxin as immunosuppressants
B G Sparkes1, J W Gyorkos, R M Gorczynski
1Defence and Civil Institute of Environmental Medicine, Downsview, Ontario, Canada.
Endotoxins of E. coli, S. typhosa and Ps. aeruginosa were injected i.p. into mice a few days before administration of the antigen sheep erythrocytes (SE). Antibody-forming cells (AFC) to SE were later enumerated in relation to dose of endotoxin given. In comparison a toxic lipid protein isolated from burned skin (cutaneous burn toxin or CBT) was similarly applied and found to be more inhibitory of the immune response than any of the three endotoxins. Considering the 50 per cent inhibitory doses on a molar basis CBT was found to be 1000 fold more immunosuppressive than the most inhibitory endotoxin. As the immune suppression which follows severe thermal injury involves failure of interleukin 2 (IL2) function, as a critical index of survival, the CBT was tested for its effects on the culture of a human IL2-dependent cell line in the presence of IL2. CBT inhibited the growth of these cells, however, endotoxin had no effect on their proliferation. Thus CBT, which arises by a thermally induced polymerization of skin lipid protein, is specific to burn injury and has a direct inhibitory effect on the immune response.
Endotoxins of E. coli, S. typhosa and Ps. aeruginosa were injected i.p. into mice a few days before administration of the antigen sheep erythrocytes (SE). Antibody-forming cells (AFC) to SE were later enumerated in relation to dose of endotoxin given. In comparison a toxic lipid protein isolated from burned skin (cutaneous burn toxin or CBT) was similarly applied and found to be more inhibitory of the immune response than any of the three endotoxins. Considering the 50 per cent inhibitory doses on a molar basis CBT was found to be 1000 fold more immunosuppressive than the most inhibitory endotoxin. As the immune suppression which follows severe thermal injury involves failure of interleukin 2 (IL2) function, as a critical index of survival, the CBT was tested for its effects on the culture of a human IL2-dependent cell line in the presence of IL2. CBT inhibited the growth of these cells, however, endotoxin had no effect on their proliferation. Thus CBT, which arises by a thermally induced polymerization of skin lipid protein, is specific to burn injury and has a direct inhibitory effect on the immune response.

