A rat model for pneumococcal otitis media

Hermansson, Ann; Emgrd, Per; Prellner, Karin; Hellström, Sten

doi:10.1016/s0196-0709(88)80013-9

Cited by 78 publications

(58 citation statements)

References 27 publications

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“…Whenever operated on or inspected under an otomicroscope, the animals were anesthetized with a rodent cocktail (13.3 mg of ketamine HCl per ml, 1.3 mg of xylazine per ml, 0.25 mg of acepromazine maleate per ml) administered intramuscularly. Inoculation was performed through the bony wall of the bulla, which was reached through a ventral midline incision and blunt dissection (16). Approximately 0.05 ml of the bacterial suspension was injected directly into to the middle ear cavities of the animals.…”

Section: Methodsmentioning

confidence: 99%

Expression of Cytokine Genes during Pneumococcal and NontypeableHaemophilus influenzaeAcute Otitis Media in the Rat

Melhus¹,

Ryan²

2000

Infect Immun

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Acute otitis media (AOM) elicits potent inflammatory responses from the cells of the middle ear mucosa as well as from infiltrating leukocytes. To explore host responses during experimental AOM induced by Streptococcus pneumoniae type 3 and nontypeable Haemophilus influenzae (NTHi), otomicroscopy findings and expression of cytokine genes in the middle ear were monitored up to 1 month postinoculation. The mucosa and infiltrating cells responded rapidly to the bacterial challenge. Otomicroscopically, AOM appeared 1 day after NTHi inoculation and 3 days after pneumococcus inoculation. Pneumococcal AOM was more severe than NTHi otitis, but in general, lower transcript levels were detected in pneumococcus-infected than in NTHi-infected animals. Interleukin-6 (IL-6) mRNA levels peaked at 3 to 6 h for both pneumococcus-infected and NTHiinfected animals. IL-1␣, tumor necrosis factor alpha, and IL-10 mRNA levels peaked at 6 h for NTHi otitis and 1 to 3 days for pneumococcal otitis. Comparing otomicroscopy with expression profiles, it would appear that the majority of cytokine mRNAs had passed their peak before the AOM diagnosis could be made clinically. Only transforming growth factor ␤ mRNA followed a slower time course, peaking very late and continuing expression even after the AOM was otomicroscopically resolved. IL-2 and IL-4 mRNAs were not detected in any animal at any time. Most of the investigated cytokines are very early markers for AOM and may be involved in initiation of inflammation, but they would be poor targets for pharmacological manipulation since their levels decline before clinical signs appear.

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Section: Methodsmentioning

confidence: 99%

Expression of Cytokine Genes during Pneumococcal and NontypeableHaemophilus influenzaeAcute Otitis Media in the Rat

Melhus¹,

Ryan²

2000

Infect Immun

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“…The rat has also been exploited for studying invasive pneumococcal disease and otitis media. Outbred strains, including Wistar, Sprague-Dawley, and CD (derived from Sprague-Dawley) rats, have been extensively utilized as experimental models (2,49,71,79,101,103,145,147,166,193,214,221,242,253). The New Zealand White rabbit is the most commonly used strain to induce pneumococcal pneumonia, sepsis, and meningitis (26,57,69,98,106,119,196,246).…”

Section: Considerations Of Animal and Pneumococcal Strainsmentioning

confidence: 99%

“…Clinical isolates of serotypes 3, 6, 9, and 19 have also been employed in laboratory animal models to elucidate features of pneumococcal pneumonia and sepsis (12,14,40,49,196,223,234,251). For experimental otitis media, strains of serotypes 3, 4, 6, 7, 9, 11, 14, 19, and 23, which are the ones most commonly isolated from children with acute otitis, have been used (18,80,81,89,101,154).…”

Section: Considerations Of Animal and Pneumococcal Strainsmentioning

confidence: 99%

“…infection. In a model described in 1988, S. pneumoniae was directly instilled into the tympanic cavities of rats to investigate bacterial replication in the ME and blood (101). Inoculation of rat ME with pneumococci caused otitis media with either purulent or serous effusion, closely resembling the disease in the human host (101).…”

Section: Rat and Mouse Modelsmentioning

confidence: 99%

“…In a model described in 1988, S. pneumoniae was directly instilled into the tympanic cavities of rats to investigate bacterial replication in the ME and blood (101). Inoculation of rat ME with pneumococci caused otitis media with either purulent or serous effusion, closely resembling the disease in the human host (101). This system has been used to evaluate the efficacy of penicillin for the treatment and prevention of permanent mucosal changes due to pneumococcal acute otitis (5,102) and to assess protection against experimental otitis media conferred either by anticapsular antibodies (256) or by active immunizations with PspA (256) or whole killed bacteria (66).…”

Section: Rat and Mouse Modelsmentioning

confidence: 99%

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Animal Models ofStreptococcus pneumoniaeDisease

2008

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SUMMARY Streptococcus pneumoniae is a colonizer of human nasopharynx, but it is also an important pathogen responsible for high morbidity, high mortality, numerous disabilities, and high health costs throughout the world. Major diseases caused by S. pneumoniae are otitis media, pneumonia, sepsis, and meningitis. Despite the availability of antibiotics and vaccines, pneumococcal infections still have high mortality rates, especially in risk groups. For this reason, there is an exceptionally extensive research effort worldwide to better understand the diseases caused by the pneumococcus, with the aim of developing improved therapeutics and vaccines. Animal experimentation is an essential tool to study the pathogenesis of infectious diseases and test novel drugs and vaccines. This article reviews both historical and innovative laboratory pneumococcal animal models that have vastly added to knowledge of (i) mechanisms of infection, pathogenesis, and immunity; (ii) efficacies of antimicrobials; and (iii) screening of vaccine candidates. A comprehensive description of the techniques applied to induce disease is provided, the advantages and limitations of mouse, rat, and rabbit models used to mimic pneumonia, sepsis, and meningitis are discussed, and a section on otitis media models is also included. The choice of appropriate animal models for in vivo studies is a key element for improved understanding of pneumococcal disease.

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