Chest
Volume 113, Issue 6, June 1998, Pages 1632-1639
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Clinical Investigations in Critical Care
Expression of Inducible Nitric Oxide Synthase and Inflammatory Cytokines in Alveolar Macrophages of ARDS Following Sepsis

https://doi.org/10.1378/chest.113.6.1632Get rights and content

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-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) in AMs obtained from RAL fluid (RALF) 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.

Section snippets

Study Population

Patients with ARDS were identified prospectively. ARDS was defined according to the definition of Murray et al12 as follows: (1) lung injury score >2.5; (2) wedge pressure <18 mm Hg measured by pulmonary catheter, or no clinical evidence of congestive heart failure; and (3) no other explanation for the above findings.12

Eight patients with sepsis (six male, two female) whose lung injury score was >2.5 in the ICU (ARDS group), eight patients (three male, five female) in the operating room soon

Composition, Albumin, and Protein Levels in the BAL

The characteristics of the BALF from each group are summarized in Table 1. The number of WBCs in the BALF from the ARDS group increased significantly as compared with that of the control group. The percentage of AMs in the BALF from the ARDS group was significantly less as compared with that of the control group. The percentage of neutrophils in the BALF from the ARDS group increased significantly as compared with that of the control group. No statistical difference was observed in the

DISCUSSION

Using an immunofluorescent technique, our study identified the strong expression of iNOS in AMs of human lungs predominantly at the early stage of ARDS following sepsis. No expression of iNOS was observed in the AMs from the control group, or the LTV group. Although the patients in both the ARDS group and the LTV group were clinically diagnosed as having sepsis syndrome, only AMs of the ARDS group whose PaO2/FIo2 was <200 immunohistochemically expressed iNOS. The stronger expressions of IL-6

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    Funded by Japanese Ministry of Education grant 200207407045 (Dr. Hashimoto).

    Reprint requests: Atsuko Kobayashi, MD, 465 Kajiicho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602, Japan

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