title: Prior elevation of IL-18 promotes rapid early IFN-gamma production during staphylococcal infection.
abstract: Systemic Staphylococcus aureus infection is associated with significant morbidity and mortality arising from both bacterial and host immune factors. IL-18 is a pro-inflammatory cytokine of the IL-1 superfamily that exhibits broad functional effects in innate and acquired immune responses and which has been found in high levels in several chronic inflammatory and autoimmune diseases. Over-expression of IL-18 may promote early resolution of infection or could promote a detrimental exaggerated immune response. This was explored in a model of S. aureus infection. We report increased mortality in Swiss mice that were given recombinant IL-18 prior to inoculation with S. aureus LS-1. IL-18 administration prior to infection induced preferentially enhanced IFN-gamma mRNA expression in peripheral blood leukocytes and spleen, especially splenic NK cells. This correlated with increased IFN-gamma protein detection in serum, and leukocyte and spleen cultures at subsequent discrete time points. These data suggest that increased mortality following gram-positive infection in autoimmune diseases could in part reflect the impact of high levels of pleiotropic pro-inflammatory cytokines such as IL-18 present prior to the onset of infection.
authors.affiliation: Department of Immunology and Bacteriology, Western Infirmary, Glasgow, UK.
authors.forename: Shauna
authors.initials: S
authors.lastname: Culshaw
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Leung
authors.forename: J Alastair
authors.initials: JA
authors.lastname: Gracie
authors.forename: Carol C
authors.initials: CC
authors.lastname: Campbell
authors.forename: Duncan
authors.initials: D
authors.lastname: Thomson
authors.forename: Curtis
authors.initials: C
authors.lastname: Gemmell
authors.forename: Foo Y
authors.initials: FY
authors.lastname: Liew
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000276:immunology*; D020382:Interleukin-18 / Q000097:blood / Q000276:immunology*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D020382:Interleukin-18; D012333:RNA, Messenger; D007371:Interferon-gamma