BAL Induces an Increase in Peripheral Blood Neutrophils and Cytokine Levels in Healthy Volunteers and Patients With Pneumonia* Takeshi Terashima, MD, PhD; Kazuhisa Amakawa, MD; Akiko Matsumaru, PhD; Stephan van Eeden, MD, PhD; James C. Hogg, MD, PhD; and Kazuhiro Yamaguchi, MD, PhD, FCCP Study objectives: To examine the peripheral effects of BAL on the neutrophil counts and cytokine levels in the circulation. Design and methods: WBC counts and plasma cytokines were measured before and 4 h after fiberoptic bronchoscopy (FOB) without further interventions (n  6), or combined with BAL in normal volunteer subjects (n  6), and in patients with bacterial pneumonia (n  4). The bronchus of the right middle lobe was wedged, and three 50-mL aliquots of sterile saline solution was instilled. There was no endotoxin contamination in the saline solution or the fluid obtained through the working channel of bronchoscope. Results: In volunteers, peripheral WBC counts and the number of nonsegmented and segmented neutrophils increased after the BAL procedure (p < 0.05) associated with the increase in plasma concentration (mean  SEM) of interleukin (IL)-6 (0.99  0.32 pg/mL before BAL and 20.38  13.42 pg/mL after BAL; p < 0.05) and granulocyte colony-stimulating factor (G-CSF; 14.1  1.7 pg/mL before BAL and 38.5  9.7 pg/mL after BAL; p < 0.05). The increase in WBC counts and neutrophil counts was positively correlated to the increase in IL-6 (p < 0.05) and the increase in G-CSF (p < 0.05). In patients with pneumonia, IL-6 and G-CSF levels were higher after BAL than in normal volunteer subjects (p < 0.05). There was no increase in plasma concentration of IL-1, tumor necrosis factor-, or IL-8 after BAL in normal volunteer subjects or in patients with pneumonia. FOB without BAL did not increase the WBC count, neutrophil count, or plasma cytokine levels. Conclusion: The BAL procedure increases the number of WBCs, and segmented and nonseg- mented neutrophils in the peripheral circulation as well as circulating IL-6 and G-CSF levels. (CHEST 2001; 119:1724 –1729) Key words: BAL; granulocyte colony-stimulating factor; interleukin-6; neutrophilia Abbreviations: ELISA = enzyme-linked immunosorbent assay; FOB = fiberoptic bronchoscopy; G-CSF = granulocyte colony-stimulating factor; GM-CSF = granulocyte-macrophage colony-stimulating factor; IL = interleukin; SIRS = systemic inflammatory response syndrome; TNF-= tumor necrosis factor- B AL is a well-established diagnostic procedure in respiratory and critical-care medicine. Side ef- fects of the procedure are fever, headache, and transient hypoxemia. 1,2 Usually, these symptoms be- gin a few hours after BAL and subside spontaneously within 1 day. It has been reported that cytokines derived from alveolar macrophages, such as tumor necrosis factor (TNF)-, interleukin (IL)-1, and IL-6, induce fever after BAL in the patients with interstitial lung diseases. 1 In these patients, the serum concentration of TNF- was high before BAL, and the patients with elevated IL-1 concen- trations before BAL were more likely to develop fever than were patients with normal cytokine values. This study suggests that the BAL procedure induces a systemic inflammatory response characterized by an increase in circulating cytokine levels. *From the Department of Internal Medicine (Dr. Terashima and Ms. Matsumaru), Tokyo Dental College Ichikawa General Hos- pital, Ichikawa, Chiba; Department of Internal Medicine (Drs. Amakawa and Yamaguchi), School of Medicine, Keio University, Shinjuku, Tokyo; and Pulmonary Research Laboratory (Drs. Eeden and Hogg), St. Pauls Hospital, Vancouver, British Colum- bia, Canada. Manuscript received June 14, 2000; revision accepted October 27, 2000. Correspondence to: Takeshi Terashima, MD, PhD, Department of Internal Medicine, Tokyo Dental College Ichikawa General Hos- pital, 5–11-13, Sugano, Ichikawa, Chiba, 272-0824, Japan; e- mail: terasima@tdc.ac.jp 1724 Clinical Investigations Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21963/ on 04/03/2017