Interleukin-1 beta and neurotrophin-3 synergistically promote neurite growth in vitro

Abstract

Pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) are considered to exert detrimental effects during brain trauma and in neurodegenerative disorders. Consistently, it has been demonstrated that IL-1β suppresses neurotrophin-mediated neuronal cell survival rendering neurons vulnerable to degeneration. Since neurotrophins are also well known to strongly influence axonal plasticity, we investigated here whether IL-1β has a similar negative impact on neurite growth. We analyzed neurite density and length of organotypic brain and spinal cord slice cultures under the influence of the neurotrophins NGF, BDNF, NT-3 and NT-4. In brain slices, only NT-3 significantly promoted neurite density and length. Surprisingly, a similar increase of neurite growth was induced by IL-1β. Additionally, both factors increased the number of brain slices displaying maximal neurite growth. Furthermore, the co-administration of IL-1β and NT-3 significantly increased the number of brain slices displaying maximal neurite growth compared to single treatments. These data indicate that these two factors synergistically stimulate two distinct aspects of neurite outgrowth, namely neurite density and neurite length from acute organotypic brain slices.

The far-reaching scope of neuroinflammation after traumatic brain injury

“…162 Elevated IL-1β also impairs LTP but surprisingly promotes neurite outgrowth and is synergistic with neurotrophin-3. 163 In rats subjected to repetitive mTBI, activation of microglia was associated with inability to induce LTP, attenuated NMDA-mediated signal, and impaired memory–these effects were not seen after single mTBI. 164 …”

MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4

“…To evaluate axonal outgrowth from the explants, we used a highly reliable evaluation procedure described previously (45), using image analysis software (ImageJ) to quantify axonal density after 2 days in culture. Neurite outgrowth was photodocumented at a total magnification of ×100, using a ×10 Olympus LCPLANFL objective (Olympus IX70).…”

AIM 2 inflammasomes regulate neuronal morphology and influence anxiety and memory in mice

“…In contrast, IL-1β at a concentration of 50 ng/ml stimulates neurite growth of enteric neurons42. High doses (500 ng/ml) of IL-1β trigger axonal growth of entorhinal cortex slice cultures, but not transverse spinal cord slice cultures43. Thus, it seems likely that different types of neurons respond differently to IL-1β in terms of axonal growth.…”