title: Prostaglandin E2 modulates monocyte MHC-II (Ia) suppression in biomaterial infection.
abstract: Staphylococcus epidermidis biomaterial infection is associated with local cellular immune suppression measured by a depressed monocyte (M phi) Ia expression. The purpose of this study was to define the effect of proinflammatory mediators on Ia expression and bacterial clearance in experimental biomaterial infection. A 1-cm-long Dacron tube graft, sterile or colonized with Staphylococcus epidermidis (1 x 10(7) cfu/ml2), was implanted in Swiss-Webster mice. Perigraft fluid was collected at 7, 10, 14, and 28 days and assayed by enzyme-linked immunoassays for tumor necrosis factor alpha (TNF alpha), interleukin (IL)-I alpha, IL-4, IL-10, and prostaglandin E2 (PGE2). Grafts were sonicated and plated for quantitative growth. In vivo effector inhibitions was accomplished with anti-TNF alpha, anti-IL-1 alpha antibodies (7 micrograms/24 hr), or indomethacin (50 micrograms/24 hr) via an Alzet 7-day microinfusion pump. M phi Ia expression was determined by flow cytometry. A significant elevation of TNF alpha, IL-1 alpha, and PGE2 was found during the first 10 days in the infected compared with sterile (P < or = 0.05) grafts and correlated with maximal Ia suppression. Neither IL-4 nor IL-10 was significantly different in the sterile or infected perigraft fluid. Indomethacin completely prevented M phi Ia suppression, while anti-IL-1 alpha only partially (94%) prevented M phi Ia suppression with a corresponding decrease in PGE2 production in infected grafts. Anti-TNF alpha increased PGE2 production by 189% and was associated with depressed M phi Ia expression. Indomethacin treatment improved mean graft-adherent bacterial clearance by 54% at 7 days and 75% at 28 days compared with control (not significant). Interleukin-1 alpha but not TNF alpha increases PGE2 production which modulates M phi Ia suppression. To improve treatment of biomaterial infections, local immunomodulation of PGE2 and IL-1 alpha is promising.
authors.affiliation: Department of Surgery, University of Louisville School of Medicine, Kentucky, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Henke
authors.forename: T M
authors.initials: TM
authors.lastname: Bergamini
authors.forename: K R
authors.initials: KR
authors.lastname: Brittian
authors.forename: H C
authors.initials: HC
authors.lastname: Polk
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D015232:Dinoprostone / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology*; D013212:Staphylococcus epidermidis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D007213:Indomethacin