Interleukin-1 As a Therapeutic Target in Acute Brain Injury

Abstract

Interest in the interactions between the immune and central nervous systems has furthered our understanding of brain function in health and disease. Experimental and clinical studies increasingly reveal an inflammatory component in the pathophysiology of many forms of brain injury. Members of the interleukin (IL)-1 cytokine family are produced by diverse cell types within the brain and may determine the outcome of neuronal injury. This review discusses the neuroprotective potential of IL-1 inhibition in various acute neurological and neurosurgical diseases. The ILs comprise an expanding family of cytokines with diverse physiological and pathological actions, of which IL-1 is a key inflammatory mediator implicated in brain injury. IL-1 expression in the normal CNS is low, but is upregulated rapidly in response to brain injury. In experimental studies, IL-1 and its endogenous, competitive, selective antagonist, IL-1 receptor antagonist (IL-1RA), mediate neurotoxic and neuroprotective outcomes, respectively. Clinical studies support the relationship between inflammation, disease severity and poor prognosis in various neurological and neurosurgical disorders. Recombinant human (rh)IL-1RA shows modest blood–brain barrier penetrance and is safe for clinical use when administered parenterally. Evidence supporting the use of rhIL-1RA and other approaches to targeting IL-1 are discussed in relation to cerebral ischemia, seizures, subarachnoid hemorrhage and traumatic brain injury.

Keywords: :

• cerebral ischemia
• cytokine
• interleukin-1
• neuroprotection
• seizure
• subarachnoid hemorrhage
• traumatic brain injury

Notes

IL: Interleukin; TNF: Tumor necrosis factor.