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Volume 11 Supplement 4

Sepsis 2007

Tolerance to lipopolysaccharide regulates apoptosis in B lymphocytes


The most important event determining sepsis evolution is immune system cell apoptosis, the immune cell elimination compromises the host effective response, and prevention of apoptosis events improve survival in sepsis models. Our objective was to identify whether lipopolysaccharide (LPS) tolerance regulates apoptotic genes and caspase pathway.

Materials and methods

Male Balb-C mice received LPS (1 mg/kg), a tolerant dose, and controls received 0.9% physiological serum during 5 days, both receiving on day 7 a LPS lethal dose (20 mg/kg). Control, 2 and 4 hours after lethal dose, IL-10, IL-6, IL-1β, TNFα and MIP2 were measured by ELISA. Splenic B lymphocytes were separated through magnetic beads and genes were analyzed by microarray, comparing control and tolerant groups. The tolerant and control groups were followed during 5 days to analyze survival.


See Table 1. The mRNA of caspases 2, 7, 8 and 11, Bid, Apaf-1 and FAS genes were reduced in the tolerant mice. The IL-6 levels reduced in the tolerant mice (724 ± 15 pg/ml) versus control mice (1,488 ± 96 pg/ml) in 2 hours. IL-1β was reduced at 0 hours and at 4 hours in the tolerant group (657 ± 25 pg/ml) versus control (1,117 ± 20 pg/ml). MIP2 also showed a reduction at 4 hours in tolerant (1,803 ± 159 pg/ml) versus control mice (2,173 ± 252 pg/ml). The tolerant animals had 100% survival, controls had zero survival. In all mentioned data, P < 0.05.

Table 1 Genic expression of apoptosis in tolerance to lipopolysaccharide


Tolerance was able to reduce cytokine plasma levels, immune cell apoptosis and mortality to LPS lethal doses.

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de Sant Anna Melo, E., Gorjao, R., Curi, R. et al. Tolerance to lipopolysaccharide regulates apoptosis in B lymphocytes. Crit Care 11 (Suppl 4), P21 (2007).

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  • Cell Apoptosis
  • Control Mouse
  • Tolerant Dose
  • Cytokine Plasma
  • Apoptotic Gene