Prolonged Elevation of IL-1 in Pseudomonas aeruginosa Ocular Infection Regulates Macrophage-Inflammatory Protein-2 Production, Polymorphonuclear Neutrophil Persistence, and Corneal Perforation

• Published in: The Journal of immunology (1950) 2000-06, Vol.164 (12), p.6576-6582
• Main Authors: Rudner, Xiaowen L, Kernacki, Karen A, Barrett, Ronald P, Hazlett, Linda D
• Format: Article
• Language: English
• Subjects: Animals; Chemokine CXCL2; Chemokines - antagonists & inhibitors; Chemokines - biosynthesis; Chemokines - genetics; Colony Count, Microbial; Corneal Ulcer - immunology; Corneal Ulcer - microbiology; Corneal Ulcer - pathology; Disease Susceptibility; Eye Infections, Bacterial - immunology; Eye Infections, Bacterial - microbiology; Eye Infections, Bacterial - pathology; Female; Immune Sera - administration & dosage; Immunity, Innate; Interleukin 1^a; Interleukin 1^b; Interleukin 1a; Interleukin 1b; Interleukin-1 - antagonists & inhibitors; Interleukin-1 - genetics; Interleukin-1 - immunology; Interleukin-1 - metabolism; Leukocyte Count; macrophage inflammatory protein 2; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neutrophils - immunology; Neutrophils - pathology; Pseudomonas aeruginosa; Pseudomonas Infections - immunology; Pseudomonas Infections - microbiology; Pseudomonas Infections - pathology; RNA, Messenger - metabolism; Rupture, Spontaneous
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.12.6576

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.