Decreased response of neutrophils from endotoxin tolerant mice towards lipopolysaccharide

MARÍA F. LÓPEZ; VERÓNICA I. LANDONI; BÁRBARA REARTE; PAULA CHIARELLA; EVANGELINA LABORDE; MARÍA V. RAMOS; LETICIA V. BENTANCOR; ROMINA J. FERNÁNDEZ-BRANDO; MARTÍN A. ISTURIZ; MARINA S. PALERMO; GABRIELA C. FERNÁNDEZ

Rio de Janeiro-Brasil

Congreso; 13th International Congress of Immunology; 2007

Septic shock is a heterogenic clinical situation associated to bacterial or fungal infection. However, 50% of the cases of sepsis are associated to infections with Gram-negative bacteria. Lipopolysaccharide (LPS) is the main component of the cell membrane of Gramnegative bacteria and it is a potent stimulator of the release of pro-inflammatory cytokines (TNF-
, IL-1, IL-8) associated to septic shock (Lehner, M., et al., 2001, Infection and Immunity, Vol. 69). The inoculation of a high dose of LPS induces pathologic symptoms similar to those observed in septic patients. However, the repetitive exposure to LPS induces a refractory state towards its effects, known as tollerance to LPS. Previous studies have demonstrated a decreased cytokine production (TNF-;, IL-1, IL-6) in monocytes pre-treated in vitro with LPS and ex vivo in monocytes from patients with sepsis (Karp, C.L., et al., 1998, Eur. J. Immunol., Vol. 28 ). Neutrophils (PMN) are central elements in the response against infectious agents and even though their activation is beneficial for the resolution of the infection, deactivation of PMN has been observed in several pathologies. In this regard, PMN from septic patients or healthy donors inoculated with LPS showed a decreased IL-8 production (Marie, C., et al., 1998, Blood, Vol. 91; Marie, C., et al., 2000, Cytokine, Vol 12).