Macrophage migration inhibitory factor, high mobility group 1 and macrophage inhibitory cytokines in meningococcal disease in children
Despite more intensive medical management and the recent anti-endotoxin and cytokine therapies the mortality and morbidity of patients with meningococcal disease (MCD) remains significant.
Dr Alistair Thomson, Dr John Sills, Dr Scott Hackett, Professor Anthony Hart
- Start Date:
01 November 2012
Alderhey Children's Hospital, Liverpool, UK
Despite more intensive medical management and the recent anti-endotoxin and cytokine therapies the mortality and morbidity of patients with meningococcal disease (MCD) remains significant. The reasons for treatment failures include, inappropriate patient selection, treatments that are unable to encompass the complex pathology of MCD and an inability to administer them soon enough after the onset of the infection. In animals MIF and HMG-1 are key components in meningococcal induced sepsis and death, their inhibitions (even up to 8 and 24 hours respectively) markedly reduce death. MIF is significantly raised in adults with 'septic shock'. If MIF and HMG-1 are raised in MCD then this opens up the possibility of new therapeutic approaches. All children admitted to Alder Hey children's hospital with suspected diagnosis of MCD over an 18-month period will be assessed. Individual patient information and data will be collected by a validated questionnaire. After informed consent, blood will be obtained with further sampling at 24 hours. Twelve hourly bloods will be taken for 48 hours from children requiring intensive care intervention. Results will be compared with a control population. MIF and HMG-1 and other cytokines will be measured by capture ELISA methods. Cortisol will be measured by a radioimmune assay. The primary outcomes will be MIF, HMG-1 levels with secondary outcomes of mortality and morbidity. All data will be stored on Microsoft Access and analysed with Excel and SPSS. Advice on the protocol design and data analysis has been given by an independent statistician.