Lin Kooi Ong, PhD

Perego C, Fumagalli S, Miteva K, Kallikourdis M, De Simoni M-G. Combined Genetic Deletion of IL (Interleukin)-4, IL-5, IL-9, and IL-13 Does Not Affect Ischemic Brain Injury in Mice. Stroke. 2019;50:2207–2215

Primary brain injury occurs immediately after the onset of stroke, and triggers a cascade of immune responses including glial activation, recruitment of peripheral immune cells and release of cytokines and chemokines. These inflammation responses may aggravate brain injury by enhancing oxidative stress, production of neurotoxic proteins and disruption of neurovascular unit. On the other hand, inflammation may also participate in waste clearance, production of neurotropic factors and support the survivor of neurons. The recognition of the crucial role of inflammation after stroke has motivated stroke researchers to investigate novel interventions to target brain inflammation processes, leading to improve neurological outcome.

Type 2 helper T cells or Th2 cells play an important role in the adaptive immune system. There is evidence that Th2 cytokines (IL-4, IL-5, IL-9 and IL-13) have neuroprotective effects. In this article, Perego and colleagues aimed to investigate the consequences of combined genetic deletion of Th2 cytokines on the neuropathophysiology after experimental stroke, by comparing wild type mice to 4KO mice. The authors found no difference in tissue loss and death of neurons at 1 week and up to 5 weeks post-stroke. However, it should be noted that the team observed lower ischemic volume in stroked 4KO mice at 24 hr, as well as changes in neuroinflammation markers at 24 hr and at 1 week. Based on the findings, the authors suggested that Th2 cytokines are not an essential neuroimmunological cue able to drive the brain’s ischemic outcome.  

While this study focused on the brain pathophysiology within the primary infarction, studies in both humans and animal models of stroke suggest that immune responses also occur in sites remote but connected to the primary injury site. Further, the authors noted that behavioural tests to investigate functional deficits were not performed. The role of Th2 cytokines in neurological recovery and brain tissue repair after stroke remains inconclusive. Future research directions in understanding Th2 cytokines after stroke should include the comparison of spatial and temporal profile and components (including microglia and infiltrating peripheral immune cells) after stroke, as well as their association to neurological outcome.

*Dr. Ong recently joined the School of Pharmacy, Monash University Malaysia.