Prior elevation of IL-18 promotes rapid early IFN-gamma production during staphylococcal infection

Culshaw, S. , Leung, B., Gracie, J., Campbell, C., Thomson, D., Gemmell, C., Liew, F. and McInnes, I. (2005) Prior elevation of IL-18 promotes rapid early IFN-gamma production during staphylococcal infection. European Journal of Immunology, 35, pp. 1438-1444. (doi: 10.1002/ejui.200425661) (PMID:15789357)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Liew, Prof Foo and Gemmell, Professor Curtis and Culshaw, Professor Shauna and Leung, Dr Bernard
• Authors: Culshaw, S., Leung, B., Gracie, J., Campbell, C., Thomson, D., Gemmell, C., Liew, F., and McInnes, I.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: European Journal of Immunology
• ISSN: 0014-2980