Prior elevation of IL-18 promotes rapid early IFN-gamma production during staphylococcal infection.
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.
Culshaw
Shauna
S
Department of Immunology and Bacteriology, Western Infirmary, Glasgow, UK.
Leung
Bernard P
BP
Gracie
J Alastair
JA
Campbell
Carol C
CC
Thomson
Duncan
D
Gemmell
Curtis
C
Liew
Foo Y
FY
McInnes
Iain B
IB
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
D020382:Interleukin-18; D012333:RNA, Messenger; D007371:Interferon-gamma