Previous Article | Next Article 
Infection and Immunity, July 2000, p. 4024-4031, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Expression of Cytokine Genes during Pneumococcal and
Nontypeable Haemophilus influenzae Acute Otitis Media in
the Rat
Åsa
Melhus* and
Allen F.
Ryan
Department of Surgery/Otolaryngology,
University of California at San Diego School of Medicine and
Veterans Affairs Medical Center, La Jolla, California
Received 21 December 1999/Returned for modification 29 February
2000/Accepted 4 April 2000
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 NTHi-infected 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.
*
Corresponding author. Present address: Department of
Medical Microbiology, Malmö University Hospital, S-205 02 Malmö, Sweden. Phone: 46 40-331350. Fax: 46 40-336234. E-mail: asa.melhus{at}mikrobiol.mas.lu.se.
Infection and Immunity, July 2000, p. 4024-4031, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Leichtle, A., Hernandez, M., Pak, K., Yamasaki, K., Cheng, C.-F., Webster, N. J., Ryan, A. F., Wasserman, S. I.
(2009). TLR4-mediated induction of TLR2 signaling is critical in the pathogenesis and resolution of otitis media. Innate Immunity
15: 205-215
[Abstract]
-
Emonts, M., Veenhoven, R. H., Wiertsema, S. P., Houwing-Duistermaat, J. J., Walraven, V., Groot, R. d., Hermans, P. W.M., Sanders, E. A.M.
(2007). Genetic Polymorphisms in Immunoresponse Genes TNFA, IL6, IL10, and TLR4 Are Associated With Recurrent Acute Otitis Media. Pediatrics
120: 814-823
[Abstract]
[Full Text]
-
Kidd, S. P., Jiang, D., Jennings, M. P., McEwan, A. G.
(2007). Glutathione-Dependent Alcohol Dehydrogenase AdhC Is Required for Defense against Nitrosative Stress in Haemophilus influenzae. Infect. Immun.
75: 4506-4513
[Abstract]
[Full Text]
-
Moon, S. K., Woo, J.-I., Lee, H.-Y., Park, R., Shimada, J., Pan, H., Gellibolian, R., Lim, D. J.
(2007). Toll-Like Receptor 2-Dependent NF-{kappa}B Activation Is Involved in Nontypeable Haemophilus influenzae-Induced Monocyte Chemotactic Protein 1 Up-Regulation in the Spiral Ligament Fibrocytes of the Inner Ear. Infect. Immun.
75: 3361-3372
[Abstract]
[Full Text]
-
Westman, E., Lundin, S., Hermansson, A., Melhus, A.
(2004). {beta}-Lactamase-Producing Nontypeable Haemophilus influenzae Fails To Protect Streptococcus pneumoniae from Amoxicillin during Experimental Acute Otitis Media. Antimicrob. Agents Chemother.
48: 3536-3542
[Abstract]
[Full Text]
-
Watanabe, T., Jono, H., Han, J., Lim, D. J., Li, J.-D.
(2004). Synergistic activation of NF-{kappa}B by nontypeable Haemophilus influenzae and tumor necrosis factor {alpha}. Proc. Natl. Acad. Sci. USA
101: 3563-3568
[Abstract]
[Full Text]
-
Wang, B., Cleary, P. P., Xu, H., Li, J.-D.
(2003). Up-Regulation of Interleukin-8 by Novel Small Cytoplasmic Molecules of Nontypeable Haemophilus influenzae via p38 and Extracellular Signal-Regulated Kinase Pathways. Infect. Immun.
71: 5523-5530
[Abstract]
[Full Text]
-
Long, J. P., Tong, H. H., Shannon, P. A., DeMaria, T. F.
(2003). Differential Expression of Cytokine Genes and Inducible Nitric Oxide Synthase Induced by Opacity Phenotype Variants of Streptococcus pneumoniae during Acute Otitis Media in the Rat. Infect. Immun.
71: 5531-5540
[Abstract]
[Full Text]
-
Tong, H. H., Long, J. P., Shannon, P. A., DeMaria, T. F.
(2003). Expression of Cytokine and Chemokine Genes by Human Middle Ear Epithelial Cells Induced by Influenza A Virus and Streptococcus pneumoniae Opacity Variants. Infect. Immun.
71: 4289-4296
[Abstract]
[Full Text]
-
Westman, E., Melhus, A.
(2002). The treatment of Haemophilus influenzae acute otitis media with amoxicillin protects against reinfection but not against structural changes. J Antimicrob Chemother
49: 141-147
[Abstract]
[Full Text]
-
Melhus, A.
(2001). Effects of amoxicillin on the expression of cytokines during experimental acute otitis media caused by non-typeable Haemophilus influenzae. J Antimicrob Chemother
48: 397-402
[Abstract]
[Full Text]
-
Shuto, T., Xu, H., Wang, B., Han, J., Kai, H., Gu, X.-X., Murphy, T. F., Lim, D. J., Li, J.-D.
(2001). Activation of NF-kappa B by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK-IKKalpha /beta -Ikappa Balpha and MKK3/6-p38 MAP kinase signaling pathways in epithelial cells. Proc. Natl. Acad. Sci. USA
10.1073/pnas.151236098v1
[Abstract]
[Full Text]
-
Tong, H. H., Chen, Y., James, M., Van Deusen, J., Welling, D. B., DeMaria, T. F.
(2001). Expression of Cytokine and Chemokine Genes by Human Middle Ear Epithelial Cells Induced by Formalin-Killed Haemophilus influenzae or Its Lipooligosaccharide htrB and rfaD Mutants. Infect. Immun.
69: 3678-3684
[Abstract]
[Full Text]
-
Shuto, T., Xu, H., Wang, B., Han, J., Kai, H., Gu, X.-X., Murphy, T. F., Lim, D. J., Li, J.-D.
(2001). Activation of NF-kappa B by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK-IKKalpha /beta -Ikappa Balpha and MKK3/6-p38 MAP kinase signaling pathways in epithelial cells. Proc. Natl. Acad. Sci. USA
98: 8774-8779
[Abstract]
[Full Text]