Cited by 110Immune Response and InflammationSepsis Diagnosis and TreatmentNeutrophil, Myeloperoxidase and Oxidative Mechanisms

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Effects of Cytokines and Endotoxin on the Intracellular Growth of Bacteria

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Kanangat, Siva, Meduri, G. Umberto, Tolley, Elizabeth A., Patterson, David R., Meduri, Christopher U., Pak, Chol, Griffin, John P., Bronze, Michael S., Schaberg, Dennis R.·1999·Infection and Immunity

DOI 10.1128/iai.67.6.2834-2840.1999PMC PMC96589

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Abstract

Patients with unresolving acute respiratory distress syndrome (ARDS) have persistently elevated levels of proinflammatory cytokines in the lungs and circulation and increased rates of bacterial infections. Phagocytic cells hyperactivated with lipopolysaccharide (LPS), which induces high levels of proinflammatory cytokines in monocytic cells, are inefficient in killing ingested bacteria despite having intact phagocytic activity. On the other hand, phagocytic cells that are activated with an analogue of LPS that does not induce the expression of proinflammatory cytokines effectively ingest and kill bacteria. We hypothesized that in the presence of high concentrations of proinflammatory cytokines, bacteria may adapt and utilize cytokines to their growth advantage. To test our hypothesis, we primed a human monocytic cell line (U937) with escalating concentrations of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-6 and with LPS. These cells were then exposed to fresh isolates of three common nosocomial pathogens: Staphylococcus aureus, Pseudomonas aeruginosa, and an Acinetobacter sp. In human monocytes primed with lower concentrations of proinflammatory cytokines (10 to 250 pg) or LPS (1 and 10 ng), intracellular bacterial growth decreased. However, when human monocytes were primed with higher concentrations of proinflammatory cytokines (1 to 10 ng) or LPS (1 to 10 micrograms), intracellular growth of the tested bacteria increased significantly (P <0.0001). These results were reproduced with peripheral blood monocytes obtained from normal healthy volunteers. The specificity of the cytokine activity was demonstrated by neutralizing the cytokines with specific antibodies. Our findings provide a possible mechanism to explain the frequent development of bacterial infections in patients with an intense and protracted inflammatory response.

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Authors: Kanangat, S., Meduri, G. U., Tolley, E. A., Patterson, D. R., Meduri, C. U., Pak, C., Griffin, J. P., Bronze, M. S., & Schaberg, D. R.
Affiliations: Department of Medicine, Pulmonary and Critical Care Division,1
Department of Preventive Medicine, Division of Biostatistics and Epidemiology,2 and
Division of Infectious Diseases,3 University of Tennessee—Memphis, Memphis, Tennessee 38163
ORCID: Meduri, G. Umberto
Tolley, Elizabeth A.
Bronze, Michael S.
Venue: Infection and Immunity
Publisher: American Society for Microbiology
Published: 1999-06
Volume: 67
Issue: 6
Pages: 2834-2840
ISSN: 0019-9567 (ISSN-L)
1098-5522
DOI: 10.1128/iai.67.6.2834-2840.1999
PMC: PMC96589
OpenAlex: W1955721074
Cited by: 110
References: 20
Citations by year: 2026: 2 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 8 · 2014: 4 · 2013: 1
FWCI: 2.05
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Infection and Immunity (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords: intracellular bacterial growth, inflammatory cytokines, lipopolysaccharide, endotoxin, acute respiratory distress syndrome, nosocomial infections, monocytes, U937 cells, TNF-α, IL-1β, interleukin-6, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter, phagocyte activation
MeSH terms: Acinetobacter, Cells, Cultured, Humans, Interleukin-1, Intracellular Fluid, Lipopolysaccharides, Monocytes, Pseudomonas aeruginosa, RNA, Messenger, Staphylococcus aureus, Tumor Necrosis Factor-alpha, Interleukin-6, Gene Expression, Cytokines, Interleukin-10, U937 Cells

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Effects of Cytokines and Endotoxin on the Intracellular Growth of Bacteria

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