In order to analyze the characteristics of the inflammatory response occurring in blood during pneumonia, we studied 38 patients with severe community-acquired pneumonia. Venous and arterial blood samples were collected at study entry and on days 1, 2, 3, 5, and 7 after inclusion. The concentrations of proinflammatory (tumor necrosis factor alpha [TNF-␣], interleukin 1␤ [IL-1␤], IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines were determined in order to detect differences related to the origin of the sample, the causative organism, the clinical variables, and the final outcome of the episode. Legionella pneumonia infections showed higher concentrations of TNF-␣, IL-6, IL-8, and IL-10. After 24 h, plasma IL-6, IL-8, and IL-10 concentrations in pneumococcal episodes increased, whereas in the same time interval, cytokine concentrations in Legionella episodes markedly decreased. The characteristics of the inflammatory response in bacteremic pneumococcal episodes were different from those in nonbacteremic episodes, as indicated by the higher plasma cytokine concentrations in the former group. Finally, our analysis of cytokine concentrations with regard to the outcome-in terms of the need for intensive care unit admittance and/or mechanical ventilation as well as mortality-suggests that there is a direct relationship between the intensity of the inflammatory response measured in blood and the severity of the episode.

Purpose: The aim of this study was to compare the evolution of systemic cytokine levels over time in patients with pneumococcal pneumonia treated either with ß-lactam monotherapy or with combination therapy (ß-lactam plus fluoroquinolone). Methods: Prospective observational study of hospitalized non-immunocompromised adults with PP. Concentrations of IL-6, IL-8, IL-10 and TNF-α were determined on days 0, 1, 2, 3, 5, and 7. Patients on ß-lactam monotherapy were compared with those receiving combination therapy. Results: Fifty-two patients were enrolled in the study. Concentrations of IL-6, IL-8, and IL-10 decreased rapidly in the first days after admission, in accordance with the mean time to defervescence. High levels of IL-6 were found in patients with the worst outcomes, measured by the need for intensive care unit admission and mortality. No major differences in demographic or clinical characteristics or severity of disease were found between patients treated with ß-lactam monotherapy or combination therapy. IL-6 levels fell more rapidly in patients with combination therapy in the first 48 hours (p=0.016). Conclusions: Our data suggest that systemic expression of IL-6 production in patients with PP is correlated with prognosis. Initial combination antibiotic therapy produces a faster decrease in this cytokine in the first 48 hours. We submitted you the revised manuscript entitled "Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia". We have taken into consideration all the reviewer's suggestions. Please find below a list of responses point by point to the reviewers' comments. Sincerely, Carolina Garcia-Vidal Infectious Diseases Service. Hospital Universitari de Bellvitge Feixa llarga s/n. 08907 L'Hospitalet, Barcelona, Spain E-mail: caroglv75@hotmail.com Fax: 34 93 2607637Comments to the Author:Reviewer #1: Prospective, non randomized study on the evolution and the impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia. A total of 52 patients enrolled. Data on the evolution of the systemic cytokine levels obtained every 24 hours during the first 5 days and on day 7. In 39 selected patients, the impact of B-lactam alone vs. Blactam plus fluoroquinolone on the systemic cytokine levels was assessed. Results showed that high levels of IL-6 at inclusion predicted the worst outcomes, including admission to ICU and mortality. In the group of patients treated with the combination, IL-6 levels fell more rapidly in the first 48 hours. COMMENTSThe study confirms previous reports that have shown a correlation of IL-6 levels at entry and prognosis. The results of the comparative study on the impact of antibiotic therapy showed that combination therapy was associated with a faster decrease in IL-6 in the first 24 and 48 hours of treatment. The Introduction, Methods and Results are appropriate and pertinent information is provided. In the Discussion, the authors elaborate considerably on the potential advantages of combination vs. monotherapy in C...