Table 3.
Role of IL-33/ST2 axis in neurological disease.
| Disease | Role of IL-33 | References |
|---|---|---|
| Alzheimer disease (AD) | • Reduced IL-33 expression in AD brain; Il33 genetic variants associate with a decrease risk in AD | (46) |
| • Increased IL-33 and ST2 in AD brains, Aβ induces IL-33 production by astrocytes to mediate AD pathogenesis | (51) | |
| • Increased sST2 in serum of AD patients; IL-33 reduces Aβ levels and amyloid plagues and reverses synaptic plasticity impairment and memory deficit in a mouse model | (52) | |
| • Effective treatment of APP/PS1 mice with improved learning and memory capability is associated with reduced level of IL-33 | (53) | |
| • IL-33 expression in astrocytes increases with age and IL-33−/− aged mice display AD-like symptoms with tau abnormality and neurodegeneration | (18) | |
| Multiple sclerosis (MS) | • Elevated IL-33 protein, mRNA levels in NAWM and plaque areas, and in plasma and PBMCs | (19, 106) |
| • Enhanced expression of IL-33 and ST2 in MS CNS lesion | (13) | |
| • mRNA of IL-33 and ST2 increased in spinal cord of EAE rats | (55) | |
| • IL-33 blockade suppresses EAE development in mice | (56) | |
| • IL-33 attenuates EAE by inducing type 2 immune response | (29) | |
| • IL-33 released by astrocytes and neurons suppresses EAE | (32) | |
| • Male-specific IL-33 attenuates EAE through ILC2s and mast cells | (57) | |
| Pain | • IL-33 is a key mediator of inflammatory hyper nociception | (87) |
| • IL-33 mediates carrageenan-induced inflammatory pain via trigging TNF-α | (88) | |
| • IL-33 induces hyperalgesia in naïve mice and enhanced hyperalgesia in a mouse model of chronic constriction injury via reciprocal relationship with TNF-α and IL-1β | (34) | |
| • IL-33 inhibits electroacupuncture analgesia in formalin mice | (92) | |
| • Spinal IL-33 and ST2 contribute to bone cancer induced pain in mice | (30) | |
| • IL-33 contributes to neuropathic pain through activating astroglial and neuronal cascades, and up-regulate NMDA | (33) | |
| • IL-33 induced by non-compressive lumber disk herniation in rat mediates pain through TNF-α, IL-1β and COX-2 | (35) | |
| Psychiatric disorders | • IL-33 polymorphism associates with decreased susceptibility to schizophrenia | (66) |
| • Serum levels of IL-33 and sST2 positively correlate with cognitive performance in schizophrenia patients, but with no difference between patients and controls | (67) | |
| • IL-33−/− mice display multiple behavioral deficits, e.g., reduced anxiety and impaired social recognition | (21) | |
| • IL-33−/− aged mice exhibit increased locomotor activities | (18) | |
| • IL-33, sST2 and IL-1β plasma levels are not changed in ASD patients | (107) | |
| • Reduced plasma IL-33 in ASD patients | (108) | |
| Stroke | • sST2 is increased in plasma of stroke patients, IL-33 protects mice against stroke through IL-4 | (81) |
| • IL-33 ameliorates brain injury in stroke model through promoting Th2 and suppressing Th17 responses | (83) | |
| • Increased serum IL-33 in acute ischemic stroke patients | (82) | |
| • IL-33/ST2 dependent microglial response limits acute ischemic brain injury | (28) | |
| Traumatic CNS injury | • Oligodendrocyte-derived IL-33 induces M2 genes and aids the recovery of optic nerve injury in mice | (12) |
| • IL-33 reduces secondary injury and improves recovery in a mouse contusion injury model through inducing Th2 and Treg responses | (31) | |
| • IL-33 improves spinal cord injury via activating meningeal ILC2s to produce type 2 cytokines | (85) | |
| Cerebral malaria | • IL-33 treatment reduces parasitaemia at early phase of infection through inducing type 2 immune responses | (39) |
| • ST2 deficient mice survived longer than WT after infection | (97) | |
| CNS encephalitis | • Levels of IL-33 protein and mRNA increased in the serum and CSF of neuro-Behcet's disease patients | (109) |
| • IL-33 attenuates viral induced encephalitis by downregulating IFN-γ and NO production | (110) | |
| CNS Toxoplasmosis | • ST2 Levels increased in brain of infected mice, ST2 deficient mice had increased susceptibility, parasite burden and encephalitis to cerebral infection | (95) |
| CNS hemorrhage | • IL-33 encoding gene Dvs 27 is active after experimental subarachnoid hemorrhage | (111) |
| • Il33 mRNA elevated in cerebral cortex in subarachnoid hemorrhage | (26) | |
| • IL-33 has neuroprotective effects in intracerebral hemorrhage in mouse | (112) |