title: Interleukin-1 receptor antagonist transiently impairs antibacterial defense but not survival in murine pneumococcal pneumonia.
abstract: The inhibition of the biological activity of IL-1 by recombinant human IL-1 receptor antagonist (IL-1ra) has been investigated in several, controlled clinical trials. Encouraging results have been reported, in particular in patients with rheumatoid arthritis. In the present study, we investigated the influence of treatment of wild type mice with IL-1ra, which resulted in an incomplete and transient inhibition of IL-1 activity. Treatment with recombinant human IL-1ra resulted in an enhanced bacterial outgrowth in the lungs of BALB/c and C57BL/6 mice early after induction of pneumococcal pneumonia, without influencing survival or the pulmonary inflammatory response. The effect of IL-1ra on the host response to S. pneumoniae pneumonia is modest and transient. The present data, together with the findings in IL-1R*/* mice in earlier work, suggest that IL-1 occupies a role in the pulmonary immune response to S. pneumoniae that is substantially less prominent than that of TNF-alpha.
authors.affiliation: Academic Medical Center, University of Amsterdam, The Netherlands. a.w.rijneveld@amc.uva.nl
authors.forename: Anita W
authors.initials: AW
authors.lastname: Rijneveld
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Peter
authors.initials: P
authors.lastname: Speelman
authors.forename: Carl K
authors.initials: CK
authors.lastname: Edwards
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D007107:Immune System / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D015996:Survival Rate; D013997:Time Factors
chemical_list: C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins