Streptococcus pneumoniae strain-dependent lung inflammatory responses in a murine model of pneumococcal pneumonia.
OBJECTIVE
The inherent properties of an invading bacterium may influence the cytokine profile that is ultimately produced. We determined the alterations in proinflammatory (TNF-alpha, 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.


METHODS
Experimental murine model of Streptococcus pneumoniae pneumonia.


METHODS
Female BALB/cby mice aged 8-10 weeks.


METHODS
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 micro l bacterial suspension of two different inocula (their respective 100% lethal inoculum and the same 10(5) 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-alpha expression varied greatly among strains, ranging from 2,643 to 10,022 pg/g and from 4 to 48 h, respectively. Moreover, TNF-alpha 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.
Mohler
Jacqueline
J
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.
Azoulay-Dupuis
Esther
E
Amory-Rivier
Cécile
C
Mazoit
Jean Xavier
JX
Bédos
Jean Pierre P
JP
Rieux
Véronique
V
Moine
Pierre
P
D000818:Animals; D019540:Area Under Curve; D004195:Disease Models, Animal; D005260:Female; D006207:Half-Life; D007249:Inflammation; D007375:Interleukin-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008171:Lung Diseases / Q000378:metabolism* / Q000503:physiopathology; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D011018:Pneumonia, Pneumococcal / Q000378:metabolism* / Q000503:physiopathology; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10