Immunology of chronic low-grade inflammation: relationship with metabolic function

Abstract

Inflammation is part of the body’s innate immune response and is an essential process that not only defends against harmful bacteria and pathogens but also plays a key role in the maintenance and repair of tissues. Under pathological conditions, there is bilateral crosstalk between immune regulation and aberrant metabolism resulting in persistent inflammation in the absence of infection. This phenomenon is referred to as sterile metabolic inflammation (metainflammation) and occurs if the initiating stimulus is not removed or if the resolution process is disrupted. Disruption of this tightly regulated immune response and its failure to resolve as is evident in metabolic disorders is not only associated with disease progression but also leads to immune senescence and should not be neglected in the clinical management of patients. This review gives an overview of the mechanisms underlying chronic metabolic inflammation, the aberrant metabolic activation of innate immune cells (neutrophils, macrophages, mast cells, dendritic cells), and its role in disease progression using obesity–diabetes as a prime example. Addressing the underlying subclinical metabolic inflammation in addition to achieving glucose control may contribute significantly towards therapeutic interventions aimed at preventing the onset of co-morbidities in diabetic patients.