Expression of Inducible Nitric Oxide Synthase in Circulating Neutrophils of the Systemic Inflammatory Response Syndrome and Septic Patients

There is increasing evidence that nitric oxide (NO) is an important factor in the pathogenesis of septic shock. It is known that polymorphonuclear neutrophils (PMNs) are activated during sepsis or after surgical stress, and they then release various toxic mediators including free radicals. It has not been clear whether NO synthesis can be induced in circulating PMNs. Blood samples were obtained from 11 patients with sepsis, 23 patients with systemic inflammatory response syndrome (SIRS), and 16 patients without SIRS (nonSIRS) who underwent operation. We examined mRNA expression of inducible NO synthase (iNOS) in circulating PMNs from those patients pre- and postoperatively using the reverse transcriptase polymerase chain reaction (RT-PCR) method and measured their serum nitrate (NO2-) + nitrate (NO3-) concentration, peripheral blood white cell (WBC) count, and serum C-reactive protein (CRP) level. The frequency of iNOS expression in PMNs increased in sepsis (100%) and SIRS (70%) patients compared to that in nonSIRS patients (18%) (p < 0.001). The peripheral WBC count and CRP level were significantly higher in iNOS-positive patients than in iNOS-negative patients (p < 0.05 and p < 0.01, respectively). Postoperatively, the serum NO2- + NO3- concentration increased in 87% of septic patients and in 56% of patients with SIRS (p < 0.05 for both). Our study indicated that iNOS mRNA expression is induced in human circulating PMNs of patients with postoperative sepsis and SIRS and may be involved in the pathogenesis of the sepsis syndrome.