SCHULTZ MJ, DE JONGE E, DEKKERS PE, VAN DEVENTER SJ, VAN DER POLL T; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 371 (abstract no. 499).

Academic Med. Ctr., Dept. of Intensive Care Med., Lab. of Experimental Internal Med., Amsterdam, NETHERLANDS

INTRODUCTION: Polymorphonuclear cells (PMNs) and mononuclear cells play a key role in inflammatory processes and during the sepsis syndrome. Mononuclear cells have been found to be hyporesponsive after stimulation with endotoxin (lipopolysaccharide, LPS) in vivo, a phenomenon reffered to as LPS tolerance. The pro-inflammatory interleukin (IL-) 8 is produced by PMNs. Aim andMETHODS: To determine the influence of an intravenous injection of LPS on the capacity of PMNs to produce IL-8 upon restimulation with bacterial products ex vivo, PMNs were isolated from 6 healthy humans directly before and at various time points after a single dose of LPS (4 ng/kg). PMNs (approximately 10[6] PMN/ml) were incubated for 24 hours at 37[0]C with 10[7] CFU/ml heat-killed Streptococcus pneumonia (HKSP), 10[7] CFU/ml heat-killed Pseudomonas aeruginosa (HKPA) and 10 ng/ml E. coli LPS. IL-8 levels were measured in supernatant (ELISA). In a separate series of experiments, PMNs from 6 other healthy volunteers (who did not receive LPS) were incubated as described above in the presence of increasing concentrations of pooled serum obtained from the LPS-challenged volunteers before (pre-LPS serum) and at various intervals after in vivo administration of LPS (post-LPS serum). Data are means +/- SE, statistics by Wilcoxon.RESULTS: The capacity of PMNs to produce IL-8 upon restimulation with HKSP, HKPA and LPS strongly decreased after in vivo exposure to LPS (production before intravenous LPS: 23.2 +/- 10.5, 2.4 +/- 0.7 and 1.8 +/- 1.4 ng/10[6] PMN, respectively; maximal inhibition to 1.7 +/- 0.3, 0.4 +/- 0.1 and 0.1 +/- 0.0 ng/10[6] PMN at 1 hour after in vivo LPS injection, respectively [all P < .05]). Production returned to normal after 24 hours. Further experiments with pooled serum demonstrated that IL-8 production by PMNs from healthy volunteers not receiving LPS, was not suppressed in the presence of increasing concentrations (0-20%) of post-LPS serum compared with pre-LPS serum.CONCLUSION: PMNs are hyporesponsive after in vivo exposure to LPS; this is not due to soluble factors produced after intravenous injection of LPS.

Publication Types:

• Meeting Abstracts

Keywords:

• Accidents
• Animals
• Endotoxins
• Humans
• Immune Tolerance
• Interleukin-8
• Lipopolysaccharides
• Neutrophils
• Pseudomonas aeruginosa
• Systemic Inflammatory Response Syndrome
• immunology
• injuries

Other ID:

• GWAIDS0007993

UI: 102245490

From Meeting Abstracts