IL-18 improves the early antimicrobial host response to pneumococcal pneumonia.
To determine the role of endogenous IL-18 during pneumonia, IL-18 gene-deficient (IL-18(-/-)) mice and wild-type (WT) mice were intranasally inoculated with Streptococcus pneumoniae, the most common causative agent of community-acquired pneumonia. Infection with S. pneumoniae increased the expression of IL-18 mRNA and was associated with elevated concentrations of both precursor and mature IL-18 protein within the lungs. IL-18(-/-) mice had significantly more bacteria in their lungs and were more susceptible for progressing to systemic infection at 24 and 48 h postinoculation. Similarly, treatment of WT mice with anti-IL-18 was associated with enhanced outgrowth of pneumococci. In contrast, the clearance of pneumococci from lungs of IL-12(-/-) mice was unaltered when compared with WT mice. Furthermore, anti-IL-12 did not influence bacterial clearance in either IL-18(-/-) or WT mice. These data suggest that endogenous IL-18, but not IL-12, plays an important role in the early antibacterial host response during pneumococcal pneumonia.
Lauw
Fanny N
FN
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Branger
Judith
J
Florquin
Sandrine
S
Speelman
Peter
P
van Deventer
Sander J H
SJ
Akira
Shizuo
S
van der Poll
Tom
T
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002455:Cell Division; D002465:Cell Movement; D018925:Chemokines / Q000096:biosynthesis; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics / Q000502:physiology; D020382:Interleukin-18 / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D013296:Streptococcus pneumoniae / Q000254:growth & development
D018925:Chemokines; D016207:Cytokines; D020382:Interleukin-18; D012333:RNA, Messenger; D018664:Interleukin-12