Effects of cytokines and endotoxin on the intracellular growth of bacteria
Open accessAbstract
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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Growth promotion of bacteria is also seen with TNFα, interleukins 1, 6, and 8, and glucocorticoids.
“as well as catecholamines, growth promotion is seen with TNFα, interleukins 1, 6, and 8, and glucocorticoids.”
From The microbiome and critical illness (2016) · cites this paper as [24]
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Self-citationMeduri, G. U. (2025) · Exploration of Endocrine and Metabolic Diseases · doi:10.37349/eemd.2025.101426 · Cited by 7 · see citing works
Self-citationUmberger, R. A., Thompson, C. L., Cashion, A. K., Kuhl, D. A., Wan, J. Y., Yates, C. R., Muthiah, M. P., & Meduri, G. U. (2015) · Dimensions of Critical Care Nursing · doi:10.1097/dcc.0000000000000098 · Cited by 7 · see citing works
Self-citationProlonged glucocorticoid treatment in ARDS: Pathobiological rationale and pharmacological principles
Meduri, G. U., Confalonieri, M., Chaudhuri, D., Rochwerg, B. N., & Meibohm, B. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-817558-3.00019-6 · Cited by 6 · see citing works
Self-citationExcessive increase of serum interleukin 6 jeopardizes host defense against multi-bacterial infection
Soda, K., Kano, Y., Kawakami, M., & Konishi, F. (2003) · Cytokine · doi:10.1016/s1043-4666(03)00108-x · Cited by 6 · see citing works
Protective effects of resolvin D1 in Pseudomonas aeruginosa keratitis
Wu, J., Gao, J., Yi, L., Gao, N., Wang, L., Zhu, J., Dai, C., Sun, L., Guo, H., Wu, X., et al. (2023) · Molecular Immunology · doi:10.1016/j.molimm.2023.04.007 · Cited by 5 · see citing works
Phagocytosis and killing of intracellular pathogens: interaction between cytokines and antibiotics
Ouadrhiri, Y., & Sibille, Y. (2000) · Current Opinion in Infectious Diseases · doi:10.1097/00001432-200006000-00006 · Cited by 5 · see citing works
Lagier, D., Platon, L., Lambert, J., Chow‐Chine, L., Sannini, A., Bisbal, M., Brun, J. P., Asehnoune, K., Léone, M., Faucher, M., et al. (2017) · Annals of Intensive Care · doi:10.1186/s13613-017-0329-7 · Cited by 4 · see citing works
Features of the lung microbiota in tuberculosis infection
Андреевна, О. Е., Огарков, О. Б., & Kolesnikova, L. I. (2024) · Bulletin of Siberian Medicine · doi:10.20538/1682-0363-2024-1-166-175 · Cited by 3 · see citing works
A Paradigm Shift: The Bidirectional Effect of Inflammation on Bacterial Growth
Meduri, G. U. (2000) · Springer eBooks · doi:10.1007/978-88-470-2284-3_16 · Cited by 3 · see citing works
Self-citationDeficiency of cannabinoid receptors enhances host susceptibility to bacterial infection
Barker, H., Bhimani, S., Tirado, D., Canas, J., Lemos, L. N., Roesch, L. F. W., & Ferraro, M. J. (2025) · mBio · doi:10.1128/mbio.02088-25 · Cited by 2 · see citing works
Quelven, Q., Grégoire, M., Coirier, V., Gacouin, A., Gallou, S. L., Cattoir, V., Cogné, M., Guegan, H., Gangneux, J., Roussel, M., et al. (2024) · Journal of Leukocyte Biology · doi:10.1093/jleuko/qiae195 · Cited by 2 · see citing works
Eukaryotic Virus Interactions with Bacteria: Implications for Pathogenesis and Control
Jones, M. K., Almand, E. A., Soorneedi, A., & Moore, M. D. (2022) · Advances in environmental microbiology · doi:10.1007/978-3-030-85395-2_10 · Cited by 2 · see citing works
Meduri, G. U. (2001) · Perspectives on critical care infectious diseases · doi:10.1007/978-1-4615-1581-4_8 · Cited by 1 · see citing works
Self-citationImmunological evaluation of Aeromonas infection in albino rats
El-Feki, M., & Awad, E. M. (2001) · Egyptian Journal of Biology · doi:10.4314/ejb.v3i2.29943 · Cited by 1 · see citing works
Microbiome in Chronic Obstructive Pulmonary Disease (COPD)
Chandran, C. S., Subin, A. J., Raj, A., Swathy, K. K., & Raghunath, I. (2022) · Springer eBooks · doi:10.1007/978-981-16-8957-4_6 · Cited by 1 · see citing works
Host Microbicidal Actions of the Innate Immune Response
Opal, S. M., & Yap, R. L. (2003) · Springer eBooks · doi:10.1007/978-1-4615-0245-6_1 · Cited by 1 · see citing works
Dysregulated Systemic Inflammation Favors Bacterial Growth and Development of Nosocomial Infections
Meduri, G. U., & Umberger, R. A. (2017) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201709-1867le · Cited by 1 · see citing works
Self-citationImmunopathogenesis of Gram-Negative Shock
Opal, S. M., & Hubert, C. E. (2005) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-47664-9_9
Choudhary, G. (2015) · Syracuse University Libraries (Syracuse University)
Chiarot, E., & Bensi, G. (2010)
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The roles of interferon regulatory factors in the murine models of colitis and sepsis
Yu, J. (2010) · Gutenberg Open Science · doi:10.25358/openscience-2232
Title: Homeostasis and its Disruption in the Lung Microbiome
Dickson, R. P., Erb‐Downward, J. R., & Huffnagle, G. B. (2015)
- 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
- <!--label omitted: 1-->Department of Medicine, Pulmonary and Critical Care Division,1
- <!--label omitted: 2-->Department of Preventive Medicine, Division of Biostatistics and Epidemiology,2 and
- <!--label omitted: 3-->Division of Infectious Diseases,3 University of Tennessee—Memphis, Memphis, Tennessee 38163
- 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
- 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
- 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 › Epidemiology › 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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