PROSTAGLANDIN E-2 MODULATES MONOCYTE MHC-II (IA) SUPPRESSION IN BIOMATERIAL INFECTION

Staphylococcus epidermidis biomaterial infection is associated with lo cal cellular immune suppression measured by a depressed monocyte (M ph i) Ia expression. The purpose of this study was to define the effect o f proinflammatory mediators on Ia expression and bacterial clearance i n experimental biomaterial infection. A l-cm-long Dacron tube graft, s terile or colonized with Staphylococcus epidermidis (1 x 10(7) cfu/ ml (2)), was implanted in Swiss-Webster mice. Perigraft fluid was collect ed at 7, 10, 14, and 28 days and assayed by enzyme-linked immunoassays for tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1 alpha , IL-4, IL-10, and prostaglandin E-2 (PGE(2)). Grafts were sonicated a nd plated for quantitative growth. In vivo effector inhibition was acc omplished with anti-TNF alpha, anti-IL-1 alpha antibodies (7 mu g/24 h r), or indomethacin (50 mu g/24 hr) via an Alzet 7-day microinfusion p ump. M phi Ia expression was determined by how cytometry. A significan t elevation of TNF alpha, IL-1 alpha, and PGE(2) was found during the first 10 days in the infected compared with sterile (P less than or eq ual to 0.05) grafts and correlated with maximal Ia suppression. Neithe r IL-4 nor IL-10 was significantly different in the sterile or infecte d perigraft fluid. Indomethacin completely prevented M phi Ia suppress ion, while anti-IL-1 alpha only partially (94%) prevented M phi Is sup pression with a corresponding decrease in PGE(2) production in infecte d grafts. Anti-TNF alpha increased PGE(2) production by 189% and was a ssociated with depressed M phi Is expression. Indomethacin treatment i mproved mean graft-adherent bacterial clearance by 54% at 7 days and 7 5% at 28 days compared with control (not significant). Interleukin-1 a lpha but not TNF alpha increases PGE(2) production which modulates M p hi Is suppression. To improve treatment of biomaterial infections, loc al immunomodulation of PGE(2) and IL-1 alpha is promising. (C) 1997 Ac ademic Press.