Immune Mechanisms Underlying Susceptibility to Endotoxin Shock in Aged Hosts: Implication in Age-Augmented Generalized Shwartzman Reaction.

In recent decades, the elderly population has been rapidly increasing in many countries. Such patients are susceptible to Gram-negative septic shock, namely endotoxin shock. Mortality due to endotoxin shock remains high despite recent advances in medical care. The generalized Shwartzman reaction is well recognized as an experimental endotoxin shock. Aged mice are similarly susceptible to the generalized Shwartzman reaction and show an increased mortality accompanied by the enhanced production of tumor necrosis factor (TNF). Consistent with the findings in the murine model, the in vitro Shwartzman reaction-like response is also age-dependently augmented in human peripheral blood mononuclear cells, as assessed by enhanced TNF production. Interestingly, age-dependently increased innate lymphocytes with T cell receptor-that intermediate expression, such as that of CD8+CD122+T cells in mice and CD57+T cells in humans, may collaborate with macrophages and induce the exacerbation of the Shwartzman reaction in elderly individuals. However, endotoxin tolerance in mice, which resembles a mirror phenomenon of the generalized Shwartzman reaction, drastically reduces the TNF production of macrophages while strongly activating their bactericidal activity in infection. Importantly, this effect can be induced in aged mice. The safe induction of endotoxin tolerance may be a potential therapeutic strategy for refractory septic shock in elderly patients.

Effects of Pasteurella multocida endotoxins on turkey poults.

Studies of turkey poult responses to Pasteurella multocida endotoxins indicated that lipopolysaccharide (LPS) preparations from two highly pathogenic strains and free endotoxin from one of these strains were all similar in lethal toxicity. Lethal intravenous doses were generally high, 1 mg or more for 1-week-old poults (13.3 mg/kg). The toxic effects of LPS were not increased by repeated administration of small hourly doses. For both forms of endotoxin, the relationship between dose and response was considered erratic. Attempts to increase the susceptibility of poults to LPS by administering a liver-damaging substance (galactosamine) or a histamine-releasing substance (compound 48/80) or by performing surgical bursectomy were not effective. The LPS did not provoke a dermal Shwartzman reaction, even though doses used were 10 times those that produced a characteristic reaction in a rabbit.