Abstract
Purpose
The objective of this study was to measure plasma cytokine levels and blood neutrophil functions as well as clinical outcomes in hospitalized patients with community-acquired pneumonia (CAP) treated with or without macrolide use—a known modulator of inflammatory response.
Methods
Subjects with CAP had peripheral blood analyzed for some neutrophil functions (degranulation of secretory vesicles and specific granules, respiratory burst response and phagocytosis) and ten cytokine levels measured in serum and sputum supernatants. Neutrophil function in healthy volunteers was also measured for reference. Values were measured on the day of enrollment, days 2–4 and 5–7, depending on a patient’s length of stay. Early and late clinical outcomes were also evaluated. All values were compared between those treated with or without a macrolide.
Results
A total of 40 subjects were in this study; 14 received macrolide treatment, and 26 did not. Neutrophil function in the macrolide group was not significantly different compared to the non-macrolide group. None of the median cytokine levels or IQRs were statistically significant between the groups. However, a trend toward decreased IL-6, IL-8, and IFN-γ levels, and favorable clinical outcomes were present in the macrolide group.
Conclusions
This pilot study showed no statistical difference between cytokine levels or neutrophil activity for CAP patients prescribed a macrolide containing regimen. Considering the trend of lower cytokine levels in the macrolide group when comparing the 5- to 7-day time period with the non-macrolide group, a full study with an appropriate sample size may be warranted.
Similar content being viewed by others
References
Hoyert DL, Xu J (2012) Deaths: preliminary data for 2011. Natl Vital Stat Rep 61:38
Mandell LA, Wunderink RG, Anzueto A et al (2007) Infectious diseases Society Of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 44(suppl2):S27–S72
Demartini G, Esposti D, Marthyn P et al (2004) Effect of multiple doses of clarithromycin and amoxicillin on IL-6, IFN-γ and IL-10 plasma levels in patients with community-acquired pneumonia. J Chemther 16:82–85
Lagrou K, Peetermans WE, Jorissen M et al (2000) Subinhibitory concentrations of erythromycin reduce pneumococcal adherence to respiratory epithelial cells in vitro. J Antimicrob Chem 46:717–723
Koch CC, Esteban DJ, Chin AC et al (2000) Apoptosis, oxidative metabolism and interleukin-8 production in human neutrophils exposed to azithromycin: effects of streptococcus pneumoniae. J Antimicrob Chem 46:19–26
Uriarte SM, Rane MJ, Luerman GC et al (2011) Granule exocytosis contributes to priming and activation of the human neutrophil respiratory burst. J Immunol 187:391–400
Haslett C, Guthrie LA, Kopaniak MM et al (1985) Modulation of multiple neutrophil functions by preparative methods or trace concentrations of bacterial lipopolysaccharide. Am J Pathol 119:101–110
Ward RA, Nakamura M, McLeish KR (2000) Priming of the neutrophil respiratory burst involves p38 mitogen-activated protein kinase-dependent exocytosis of flavocytochrome b558-containing granules. J Biol Chem 275:36713–36719
Fernandez-Botran R, Uriarte SM, Arnold FW et al (2014) Contrasting inflammatory responses in severe and non-severe community-acquired pneumonia. Inflammation 37:1158–1166
Khair OA, Devalia JL, Abdelaziz MM et al (1995) Effect of erythromycin on haemophilus influenzae endotoxin-induced release of il-6, il-8 and sicam-1 by cultured human bronchial epithelial cells. Eur Resp J 8:1451–1457
Rios AM, Mejias A, Chavez-Bueno S et al (2004) Impact of cethromycin (abt-773) therapy on microbiological, histologic, immunologic, and respiratory indices in a murine model of mycoplasma pneumoniae lower respiratory infection. Antimicrob Agents Chemother 48:2897–2904
Rios AM, Fonseca-Aten M, Mejias A et al (2005) Microbiologic and immunologic evaluation of a single high dose of azithromycin for treatment of experimental mycoplasma pneumoniae pneumonia. Antimicrob Agents Chemother 49:3970–3973
Rodrigo C, Mckeever TM, Woodhead M et al (2013) Single versus combination antibiotic therapy in adults hospitalised with community acquired pneumonia. Thorax 68:493–495
Arnold FW, Summersgill JT, Lajoie AS et al (2007) A worldwide perspective of atypical pathogens in community-acquired pneumonia. Am J Resp Crit Care Med 175:1086–1093
Kovaleva A, Remmelts HHF, Rijkers GT et al (2012) Immunomodulatory effects of macrolides during community-acquired pneumonia. J Antimicrob Chemother 67:530–540
Restrepo MI, Mortensen EM, Waterer GW et al (2009) Impact of macrolide therapy on mortality for patients with severe sepsis due to pneumonia. Eur Resp J 33:153–159
Martin-Loeches I, Lisboa T, Rodriguez A et al (2010) Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia. Intensive Care Med 36:612–620
Asadi L, Sligl WI, Eurich DT et al (2012) Macrolide-based regimens and mortality in hospitalized patients with community-acquired pneumonia: a systematic review and meta-analysis. Clin Infect Dis 55:371–380
Yanagihara K, Izumikawa K, Higa F et al (2009) Efficacy of azithromycin in the treatment of community-acquired pneumonia, including patients with macrolide-resistant streptococcus pneumoniae infection. Internal Med 48:527–535
Acknowledgments
This material is based upon work approved by the University of Louisville Hospital and the Department of Veteran Affairs Offices of Research and Development, as well as the Veterans Health Administration. This work was unfunded.
Author information
Authors and Affiliations
Consortia
Corresponding author
Ethics declarations
Conflict of Interest
The authors have no disclosures.
Research Involving Animal and Human Rights
This research involved humans.
Informed Consent
Informed consent was obtained.
Additional information
For the Community-Acquired Pneumonia Inflammatory Study Group.
Rights and permissions
About this article
Cite this article
Arnold, F.W., Bordon, J., Fernandez-Botran, R. et al. Macrolide Use and Neutrophil Function/Cytokine Levels in Hospitalized Patients with Community-Acquired Pneumonia: A Pilot Study. Lung 194, 155–162 (2016). https://doi.org/10.1007/s00408-015-9822-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00408-015-9822-7