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Infection and Immunity, June 1999, p. 2834-2840, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Effects of Cytokines and Endotoxin on the Intracellular Growth of Bacteria

Siva Kanangat,1,* G. Umberto Meduri,1 Elizabeth A. Tolley,2 David R. Patterson,1 Christopher U. Meduri,1 Chol Pak,1 John P. Griffin,1 Michael S. Bronze,3 and Dennis R. Schaberg3

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

Received 11 September 1998/Returned for modification 2 November 1998/Accepted 12 March 1999

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 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.

* Corresponding author. Mailing address: Memphis Lung Research Program, University of Tennessee---Memphis, 956 Court Ave., Room H316, Memphis, TN 38163. Phone: (901) 448-1475. Fax: (901) 448-7726. E-mail: skanangat{at}utmem.edu.

Infection and Immunity, June 1999, p. 2834-2840, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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