The role of cytokines in inflammation and infection

Dr. Eddy F Y Liew

Gardiner Professor of Immunology

University of Glasgow, UK

Abstract

Cytokines are hormones of the immune system. Cytokine-targeting represents a major triumph in immunology scientifically, clinically and commercially. There is therefore considerable interest in discovering novel cytokines. I will illustrate the pleiotropic role of some of the novel cytokines by focusing on interleukin (IL)-33.

Alzheimer’s disease is characterized by an accumulation of b-amyloid in the brain that triggers chronic neuroinflammation that leads to microglia activation, and synaptic and neuronal dysfunction. Systemic injection of IL-33 reversed synaptic plasticity impairment and cognitive deficits in APP/PS1 mice (a model of Alzheimer’s disease), reduced soluble b-amyloid levels and amyloid plaque deposition by promoting the recruitment and uptake of b-amyloid by microglia. In addition IL-33 modulates the innate immune response by polarizing microglia towards an anti-inflammatory phenotype and reducing the expression of pro-inflammatory genes, such as Nlrp3, IL-1β and IL-6 in the cortices of APP/PS1 mice. In humans, IL-33 expression was decreased in the brain of patients with Alzheimer’s disease, and levels of serum sST2 are elevated in patients with mild cognitive impairment. Therefore, mobilization of innate immunity by IL-33 to prevent and clear established β-amyloid accumulation represents a new treatment paradigm for Alzheimer’s disease

Cerebral malaria is a devastating disease affecting children under 5 with 80% mortality. Furthermore, the survivors frequently (30%) suffer from cognitive impairment. A combination treatment of IL-33 with artesunate potently attenuated experimental cerebral malaria (ECM) in mice, with 100% survival and markedly reduced cognitive dysfunction. IL-33 reduces cerebral inflammation by blocking NLRP3 in the inflammasome pathway. Furthermore, a chemical inhibitor of NLRP3 mimics the effect of IL-33. Thus a combination of artesunate and NLRP3 inhibition is a promising new approach for treatment of cerebral malaria, a devastating condition with unmet clinical need.

Time: 14:00-15:30, April 24th (Wednesday)

Venue: Room D326, Medical Science Building

Host: Dr. Wenwen Zeng