Sepsis and interleukin-6: detecting a dysregulated response to infection

National Institute for Health and Care Excellence (NICE) guideline NG51¹ defines sepsis as a life-threatening organ dysfunction due to a dysregulated host response to infection. Early diagnosis of sepsis is essential and a number of biomarkers have been proposed that could help with clinical decision-making. Nevertheless, the overall diagnostic effectiveness of these biomarkers depends on many factors including age of the patient, the cause of infection, and the sample type. For example, measurements of cytokine level in suspected neonatal sepsis could be obtained from the patient’s serum, cord blood, amniotic fluid or maternal blood, each giving different sensitivities and specificities for the same biomarker.

Sepsis claims 1000 lives each week in the UK and is one of the leading causes of avoidable deaths, more than bowel, prostate and breast cancer combined, costing the NHS £2 billion a year.² With at least 16 diagnostic companies supplying sepsis diagnostic kits and reagents, the sepsis diagnostic market is forecast to be worth over £500 million by 2025, driven by the global increase in prevalence of hospital-acquired infections (HAIs), antibiotic resistance, ageing population, health awareness and the rising number of surgical procedures.

            Sepsis has been considered a biphasic system comprising i) a pro-inflammatory response (cytokine storm) of interleukin (IL)-6, IL-8, tumour necrosis factor-α (TNFα), and recruitment of the adaptive immune components; and ii) a compensatory anti-inflammatory response system (CARS) – a systemic deactivation of the immune system to restore homeostasis, probably mediated by IL-10. However, there is evidence that both pro- and anti-inflammatory cytokines are produced and secreted concurrently during sepsis. A persistent anti-inflammatory response leads to immunosuppression carrying an increased risk of recurring and secondary infection (Fig 1).