Expression of inducible nitric oxide synthase and inflammatory cytokines in alveolar macrophages of ARDS following sepsis

Abstract

Study objective: The objective of this study was to evaluate the role of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines in alveolar macrophages (AMs) in the pathogenesis of ARDS following sepsis.

Setting: ICU in a university hospital.

Design: Prospective exploratory, open-labeled study was carried out.

Patients: A total of 24 patients were investigated: 8 patients diagnosed as having ARDS following sepsis (ARDS group); 8 patients under general anesthesia in the operating room whose lung functions were normal (control group); and 8 patients who were intubated and artificially ventilated for 1 week in the ICU whose lung functions were not deteriorated without fulfilling the ARDS criteria and whose general state fulfilled the sepsis criteria (long-term ventilation group, or LTV group).

Measurements and results: The expression of iNOS, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) in AMs obtained from BAL fluid (BALF) was determined by the immunofluorescent technique. We observed the significant expression of iNOS, IL-6, and IL-8 only in the ARDS group. Meanwhile, NOx (the sum of NO2- + NO3-) was elevated in the BALF supernatant, and IL-6 and IL-8 levels in both the BALF supernatant and the serum were also elevated in the ARDS group. No significant expressions were detected in the control and the LTV group.

Conclusions: The result that iNOS was detected only in ARDS patients following sepsis suggests that iNOS together with proinflammatory cytokines produced by AMs might play a pivotal role in the pathogenesis of acute lung injury and be useful for monitoring disorders in the lung in such conditions.