Exposure to endotoxin produces a state of macrophage hyporesponsiveness on subsequent stimulation. Monocytes in patients with septic shook demonstrate a similar hyporesponsiveness to endotoxin. The purpose of this study was to examine whether this state of hyporesponsiveness extends to other inflammatory stimuli and the relationship of this state to cell surface receptor expression and the release of anti-inflammatory cytokines. Twelve normal volunteers, 10 patients with severe sepsis, and 9 patients with septic shook were included in the study. Monocytes from each subject were isolated and stimulated with lipopolysaccharide (LPS), staphylococcal enterotoxin B (SEB), and phorbol myristate acetate (PMA). Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). Serum levels of transforming growth factor-β1 (TGF-β1), prostaglandin E2 (PGE2), and interleukin-10 (IL-10) were also measured by ELISA. The expression of monocyte CD14 and HLA-DR in whole blood were measured by flow cytometry. Patients with septic shook demonstrated significantly decreased TNF-α and IL-1β release as compared with normal subjects in response to LPS. In response to SEB, patients with sepsis and patient with septic shook demonstrated significantly decreased release of TNF-α and IL-1β. Significant decreases in TNF-α release were found in the patients with septic shook after PMA stimulation. There were no significant differences in the monocyte response to the different stimuli between patients with gram-positive sepsis and gram-negative sepsis. HLA-DR expression was significantly decreased in patients with septic shook (58 ± 9 fluorescence units (flU)) as compared with normal subjects (102 ± 14 flU) (p < 0.05). No differences in CD14 expression were observed. IL-10 levels were significantly increased in patients with sepsis (16 ± 4 pg/ml) and in patients with septic shook (42 ± 15 pg/ml) and were detectable in 1 normal subject. TGF-β1 levels were decreased in patients with septic shook (25 ± 6 pg/ml) as compared with those in normal subjects (37 ± 2 pg/ml)(p < 0.05). PGE2 levels were significantly increased in patients with septic shook and patients with sepsis. These data are consistent with a more generalized monocyte hyporesponsiveness to bacterial toxins that may be related to altered cell surface receptor expression and the release of anti-inflammatory cytokines.
ASJC Scopus subject areas
- Pathology and Forensic Medicine