Effects of cytokines and endotoxin on the intracellular growth of bacteria

Siva Kanangat, Gianfranco Meduri, Elizabeth Tolley, David R. Patterson, Christopher U. Meduri, Chol Pak, John P. Griffin, Michael S. Bronze, Dennis R. Schaberg

Research output: Contribution to journalArticle

75 Citations (Scopus)

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-1β (IL-1β), 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 μg), 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.

Original languageEnglish (US)
Pages (from-to)2834-2840
Number of pages7
JournalInfection and Immunity
Volume67
Issue number6
StatePublished - Jun 1 1999

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Endotoxins
Cytokines
Bacteria
Growth
Lipopolysaccharides
Monocytes
Phagocytes
Bacterial Infections
Healthy Volunteers
Acinetobacter
Adult Respiratory Distress Syndrome
Interleukin-1
Pseudomonas aeruginosa
Staphylococcus aureus
Interleukin-6
Tumor Necrosis Factor-alpha
Cell Line
Lung
Antibodies

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Kanangat, S., Meduri, G., Tolley, E., Patterson, D. R., Meduri, C. U., Pak, C., ... Schaberg, D. R. (1999). Effects of cytokines and endotoxin on the intracellular growth of bacteria. Infection and Immunity, 67(6), 2834-2840.

Effects of cytokines and endotoxin on the intracellular growth of bacteria. / Kanangat, Siva; Meduri, Gianfranco; Tolley, Elizabeth; Patterson, David R.; Meduri, Christopher U.; Pak, Chol; Griffin, John P.; Bronze, Michael S.; Schaberg, Dennis R.

In: Infection and Immunity, Vol. 67, No. 6, 01.06.1999, p. 2834-2840.

Research output: Contribution to journalArticle

Kanangat, S, Meduri, G, Tolley, E, Patterson, DR, Meduri, CU, Pak, C, Griffin, JP, Bronze, MS & Schaberg, DR 1999, 'Effects of cytokines and endotoxin on the intracellular growth of bacteria', Infection and Immunity, vol. 67, no. 6, pp. 2834-2840.
Kanangat S, Meduri G, Tolley E, Patterson DR, Meduri CU, Pak C et al. Effects of cytokines and endotoxin on the intracellular growth of bacteria. Infection and Immunity. 1999 Jun 1;67(6):2834-2840.
Kanangat, Siva ; Meduri, Gianfranco ; Tolley, Elizabeth ; Patterson, David R. ; Meduri, Christopher U. ; Pak, Chol ; Griffin, John P. ; Bronze, Michael S. ; Schaberg, Dennis R. / Effects of cytokines and endotoxin on the intracellular growth of bacteria. In: Infection and Immunity. 1999 ; Vol. 67, No. 6. pp. 2834-2840.
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