title: IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection.
abstract: Secondary pneumococcal pneumonia is a serious complication during and shortly after influenza infection. We established a mouse model to study postinfluenza pneumococcal pneumonia and evaluated the role of IL-10 in host defense against Streptococcus pneumoniae after recovery from influenza infection. C57BL/6 mice were intranasally inoculated with 10 median tissue culture infective doses of influenza A (A/PR/8/34) or PBS (control) on day 0. By day 14 mice had regained their normal body weight and had cleared influenza virus from the lungs, as determined by real-time quantitative PCR. On day 14 after viral infection, mice received 10(4) CFU of S. pneumoniae (serotype 3) intranasally. Mice recovered from influenza infection were highly susceptible to subsequent pneumococcal pneumonia, as reflected by a 100% lethality on day 3 after bacterial infection, whereas control mice showed 17% lethality on day 3 and 83% lethality on day 6 after pneumococcal infection. Furthermore, 1000-fold higher bacterial counts at 48 h after infection with S. pneumoniae and, particularly, 50-fold higher pulmonary levels of IL-10 were observed in influenza-recovered mice than in control mice. Treatment with an anti-IL-10 mAb 1 h before bacterial inoculation resulted in reduced bacterial outgrowth and markedly reduced lethality during secondary bacterial pneumonia compared with those in IgG1 control mice. In conclusion, mild self-limiting influenza A infection renders normal immunocompetent mice highly susceptible to pneumococcal pneumonia. This increased susceptibility to secondary bacterial pneumonia is at least in part caused by excessive IL-10 production and reduced neutrophil function in the lungs.
authors.affiliation: Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Koenraad F
authors.initials: KF
authors.lastname: van der Sluijs
authors.forename: Leontine J R
authors.initials: LJ
authors.lastname: van Elden
authors.forename: Monique
authors.initials: M
authors.lastname: Nijhuis
authors.forename: Rob
authors.initials: R
authors.lastname: Schuurman
authors.forename: Jennie M
authors.initials: JM
authors.lastname: Pater
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Michel
authors.initials: M
authors.lastname: Goldman
authors.forename: Henk M
authors.initials: HM
authors.lastname: Jansen
authors.forename: René
authors.initials: R
authors.lastname: Lutter
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis; D004198:Disease Susceptibility / Q000209:etiology; D005260:Female; D007109:Immunity; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008168:Lung / Q000737:chemistry / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D009976:Orthomyxoviridae Infections / Q000150:complications*; D011018:Pneumonia, Pneumococcal / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D013296:Streptococcus pneumoniae / Q000254:growth & development; D015996:Survival Rate
chemical_list: D000906:Antibodies; D016207:Cytokines; D016753:Interleukin-10