Co-administration of these peptides with Aβ<sub>25-35</sub> to glial cultures increased IL-4 and reduced IL-1β; this release of IL-4 could be responsible for activation of Akt and increased somatostatin in neuronal cultures.
Colchicine is still the only approved drug for the prevention of amyloidosis in FMF and utility of IL-1 inhibitors in crFMF cases who already has amyloidosis remain to be elucidated.
IL-1 blockade induced disease remission in all individuals while hearing mildly improved or remained stable in affected patients as did renal function in one surviving individual with amyloidosis.
Immunohistochemistry was performed to assess interleukin-1β (IL-1β) and islet hormone (insulin, glucagon, somatostatin, and pancreatic polypeptide) immunoreactivity; histochemistry was performed to quantify amyloid deposition.
We used a combination of in vitro (Bv2 microglial cell cultures) and in vivo (mice injected with amyloid-β (Aβ)) techniques to address the role of caspase-1 activation in release of IL-1β.
Similarly, using a mouse model of hippocampal deafferentation without amyloidosis, (i.e., the entorhinal cortex lesioned mouse), we observed significant increases in the expression of both the Tlr4 (p = 0.0367 and p = 0.0193 compared to sham-lesioned mice or to the contralateral side, respectively) and Il1b (p = 0.0055 and p = 0.0066 compared to sham-lesioned mice or to the contralateral side, respectively) genes in the deafferentation phase, but not during the ensuing reinnervation process.
Using electrophysiological techniques we longitudinally studied the effects of the NLRP3 inflammasome inhibitor Mcc950, the IL-1 receptor antagonist (anakinra) and an anti-TNF-α agent (etanercept) in awake freely moving transgenic rats overexpressing AD associated β-amyloid precursor protein at a pre-plaque stage of amyloidosis.
We found that ANDRO significantly protected neuronal cells against microglia-mediated Aβ(1-42) toxicity and attenuated the release of preinflammatory productions such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nitric oxide (NO), and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>).
In the hippocampus, minocycline reversed the increases in the levels of interleukin (IL-1β), Tumor Necrosis Factor- alpha (TNF-α) and, IL-10 caused by Aβ (1-42).
Brain tissues were collected to measure Aβ levels (Aβ<sub>1-40</sub> and Aβ<sub>1-42</sub>), acetylcholine (ACh), acetylcholinesterase (AChE), nitric oxide (NO), lipid peroxidation (LPO), antioxidant activities, cyclooxygenases (COX) and cytokines (IL-1α, IL-1β and IL-6), while plasma was collected to measure TGF-1β.
Nowadays, the use of anti-IL-1 drugs has sensibly reduced the risk of developing main complications such as severe intellectual disability, hearing-loss and amyloidosis, if treatment is started early on.
Reduced amyloidosis in bigenic mice was concomitant with decreased glial reactivity and interleukin-1β (IL-1β) levels, and the preservation of long-term potentiation (LTP) and spatial learning, without changes in the activity of α-, β- and γ-secretases.
In particular, overexpression of the dominant-negative form of RAGE targeted to microglia (DNMSR) protects against OGD-induced synaptic impairment in an amyloid-enriched environment, reducing the activation of stress-related kinases (p38MAPK and JNK) and the release of IL-1β.