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Streptococcus pneumoniae strain-dependent lung inflammatory responses in a murine model of pneumococcal pneumonia

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Abstract

Objective

The inherent properties of an invading bacterium may influence the cytokine profile that is ultimately produced. We determined the alterations in proinflammatory (TNF-α, IL-1, and IL-6) and anti-inflammatory cytokine (IL-10) expressions in lung tissues within the first 48 h after infection in mice with pneumonia induced by direct intratracheal inoculation of five different pneumococcal strains.

Design

Experimental murine model of Streptococcus pneumoniae pneumonia.

Subjects

Female BALB/cby mice aged 8–10 weeks.

Interventions

Five S. pneumoniae clinical isolates were used in this study. The strains included two serotype 3 strains (P4241 and P30606), two serotype 6 strains (P26772 and P23477), and one serotype 19 strain (P15986). The trachea of anesthetized animals was cannulated via the mouth with a blunt needle, and 50 µl bacterial suspension of two different inocula (their respective 100% lethal inoculum and the same 105 CFU/mouse inoculum of S. pneumoniae strains) were instillated. At predetermined times after pneumococcal infection, i.e., time 0 (preinfection) and 2, 4, 6, 12, 24, and 48 h postinfection in experimental groups, lung tissues were sampled from groups of three mice to quantify lung pro- and anti-inflammatory mediators. The experiments were repeated at least three times.

Results

Pneumonia induced by five different pneumococcal isolates resulted in pronounced differences in the local pro- and anti-inflammatory profiles. For example, with a 100% lethal inoculum of S. pneumoniae, the extent and timing of TNF-α expression varied greatly among strains, ranging from 2,643 to 10,022 pg/g and from 4 to 48 h, respectively. Moreover, TNF-α productions within 48 h postinfection measured by the 48 h area under the curve were differed significantly, ranging from 59,700 to 275,825. These different profiles were not serotype dependent. Comparable results were obtained when IL-1, IL-6, and IL-10 expressions in lung tissues were studied.

Conclusions

These findings confirm that the production of the pro- and anti-inflammatory mediators are critically dependent not only upon the different species of bacteria used to establish the experimental infection but also upon the different strains of a specific bacterial species used, i.e., S. pneumoniae in this study. These substantially different host responses were not serotype dependent. Moreover, the profile of lung pro-and anti-inflammatory cytokines within 48 h postinfection, at least in this pneumonia model, was not related to outcome of animals.

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Authors and Affiliations

  1. Département d'Anesthésie Réanimation, Hôpital Lariboisière, 2 rue Ambroise Paré, 75745, Paris cedex 10, France

    Pierre Moine

  2. Institut National de la Santé et de la Recherche Médicale, EMI-U 9933, Bâtiment U13, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75877, Paris Cedex 18, France

    Jacqueline Mohler, Esther Azoulay-Dupuis, Cécile Amory-Rivier, Jean Pierre P. Bédos, Véronique Rieux & Pierre Moine

  3. Département d'Anesthésie Réanimation et Laboratoire d'Anesthésie, UPRES EA392, CHU de Bicêtre, Université Paris-Sud, 78 Rue du Général Leclerc, 94275, le Kremlin-Bicêtre cedex, France

    Jean Xavier Mazoit

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  1. Jacqueline Mohler
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  2. Esther Azoulay-Dupuis
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  3. Cécile Amory-Rivier
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  4. Jean Xavier Mazoit
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  5. Jean Pierre P. Bédos
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  6. Véronique Rieux
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  7. Pierre Moine
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Corresponding author

Correspondence to Pierre Moine.

Additional information

J. Mohler and P. Moine contributed equally to this work.

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Mohler, J., Azoulay-Dupuis, E., Amory-Rivier, C. et al. Streptococcus pneumoniae strain-dependent lung inflammatory responses in a murine model of pneumococcal pneumonia. Intensive Care Med 29, 808–816 (2003). https://doi.org/10.1007/s00134-003-1699-x

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  • DOI: https://doi.org/10.1007/s00134-003-1699-x

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