BACKGROUND: We previously reported enhanced expression of nuclear factor kappa B (NF-kappaB) in activated polymorphonuclear leukocytes (PMNLs) from patients with systemic inflammatory response syndrome (SIRS). Inflammatory response, however, is not regulated only by stimulatory transcription factors. Glucocorticoid receptor (GR) has been recently reported to play an important role in anti-inflammatory signal transduction. The objective of our study was to evaluate the balance between expression of intranuclear NF-kappaB and GR in PMNLs from SIRS patients. METHODS: In study 1, 29 patients with severe SIRS, who fulfilled the criteria for SIRS and had a serum C-reactive protein level of more than 10 mg/dL, were included. Expression of intranuclear NF-kappaB and GR in PMNLs was measured by flow cytometry with antibodies specific for NF-kappaB subunit p65 and GR. PMNL oxidative activity and serum cytokine levels were also measured. Study 2 included 13 patients with severe trauma (Injury Severity Score 24.6 +/- 12.2). We measured serial changes in expression of intranuclear NF-kappaB and GR in days 0 to 2, 3 to 6, and 7 to 14 after injury. RESULTS: In study 1, expression of both intranuclear NF-kappaB and GR in PMNLs was significantly higher in SIRS patients than in healthy controls. There was a strong correlation between expression of these two transcription factors (r = 0.78). Positive correlations were also found between PMNL oxidative activity and both transcription factors. In study 2, expression of both NF-kappaB and GR in PMNLs was markedly elevated on days 3 to 6 after injury and changed serially with strong mutual correlation. CONCLUSIONS: In activated PMNLs from SIRS patients, levels of both intranuclear NF-kappaB and GR were elevated and strongly correlated. In trauma patients, NF-kappaB and GR in PMNLs changed serially with strong mutual correlation. Further studies are needed to clarify the effect of the balance of NF-kappaB and GR on PMNL activation and systemic inflammatory process.
BACKGROUND: We previously reported enhanced expression of nuclear factor kappa B (NF-kappaB) in activated polymorphonuclear leukocytes (PMNLs) from patients with systemic inflammatory response syndrome (SIRS). Inflammatory response, however, is not regulated only by stimulatory transcription factors. Glucocorticoid receptor (GR) has been recently reported to play an important role in anti-inflammatory signal transduction. The objective of our study was to evaluate the balance between expression of intranuclear NF-kappaB and GR in PMNLs from SIRS patients. METHODS: In study 1, 29 patients with severe SIRS, who fulfilled the criteria for SIRS and had a serum C-reactive protein level of more than 10 mg/dL, were included. Expression of intranuclear NF-kappaB and GR in PMNLs was measured by flow cytometry with antibodies specific for NF-kappaB subunit p65 and GR. PMNL oxidative activity and serum cytokine levels were also measured. Study 2 included 13 patients with severe trauma (Injury Severity Score 24.6 +/- 12.2). We measured serial changes in expression of intranuclear NF-kappaB and GR in days 0 to 2, 3 to 6, and 7 to 14 after injury. RESULTS: In study 1, expression of both intranuclear NF-kappaB and GR in PMNLs was significantly higher in SIRS patients than in healthy controls. There was a strong correlation between expression of these two transcription factors (r = 0.78). Positive correlations were also found between PMNL oxidative activity and both transcription factors. In study 2, expression of both NF-kappaB and GR in PMNLs was markedly elevated on days 3 to 6 after injury and changed serially with strong mutual correlation. CONCLUSIONS: In activated PMNLs from SIRS patients, levels of both intranuclear NF-kappaB and GR were elevated and strongly correlated. In traumapatients, NF-kappaB and GR in PMNLs changed serially with strong mutual correlation. Further studies are needed to clarify the effect of the balance of NF-kappaB and GR on PMNL activation and systemic inflammatory process.
Authors: Erica L T van den Akker; Carla C Baan; Bart van den Berg; Henk Russcher; Koen Joosten; Anita C S Hokken-Koelega; Steven W J Lamberts; Jan W Koper Journal: Intensive Care Med Date: 2008-01-08 Impact factor: 17.440