title: Prolonged elevation of IL-1 in Pseudomonas aeruginosa ocular infection regulates macrophage-inflammatory protein-2 production, polymorphonuclear neutrophil persistence, and corneal perforation.
abstract: The kinetics of IL-1 (alpha and beta) production after Pseudomonas aeruginosa corneal infection was examined in susceptible (cornea perforates) C57BL/6J (B6) and resistant (cornea heals) BALB/cByJ (BALB/c) mice. IL-1alpha and -1beta (mRNA and protein) were elevated in both mouse strains, and levels peaked at 1 day postinfection (p.i. ). Significantly greater amounts of IL-1 protein were detected in B6 vs BALB/c mice at 1 and 3 days p.i. At 5 days p.i., IL-1alpha and -1beta (mRNA and protein) remained elevated in B6, but began to decline in BALB/c mice. To test the significance of elevated IL-1 in B6 mice, a polyclonal neutralizing Ab against IL-1beta was used to treat infected B6 mice. A combination of subconjunctival and i.p. administration of IL-1beta polyclonal Ab significantly reduced corneal disease. The reduction in disease severity in infected B6 mice was accompanied by a reduction in corneal polymorphonuclear neutrophil number, bacterial load, and macrophage inflammatory protein-2 mRNA and protein levels. These data provide evidence that IL-1 is an important contributor to P. aeruginosa corneal infection. At least one mechanism by which prolonged and/or elevated IL-1 expression contributes to irreversible corneal tissue destruction appears to be by increasing macrophage inflammatory protein-2 production, resulting in a prolonged stimulation of polymorphonuclear neutrophil influx into cornea. In contrast, a timely down-regulation of IL-1 appears consistent with an inflammatory response that is sufficient to clear the bacterial infection with less corneal damage.
authors.affiliation: Department of Anatomy/Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: X L
authors.initials: XL
authors.lastname: Rudner
authors.forename: K A
authors.initials: KA
authors.lastname: Kernacki
authors.forename: R P
authors.initials: RP
authors.lastname: Barrett
authors.forename: L D
authors.initials: LD
authors.lastname: Hazlett
mesh_terms: D000818:Animals; D054426:Chemokine CXCL2; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015169:Colony Count, Microbial; D003320:Corneal Ulcer / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004198:Disease Susceptibility; D015818:Eye Infections, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage; D007113:Immunity, Innate; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012422:Rupture, Spontaneous
chemical_list: D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D007106:Immune Sera; D007375:Interleukin-1; D012333:RNA, Messenger