Administration of branched-chain amino acids alters the balance between pro-inflammatory and anti-inflammatory cytokines

Acute leucine intoxication and neurologic deterioration can develop rapidly at any age as a result of net protein degradation precipitated by infection or psychological stress in patients with maple syrup urine disease (MSUD). Here, we investigated the effects of acute and chronic Hyper-BCAA (H-BCAA) administration on pro- and anti-inflammatory cytokines in the brains of rats. For acute administration, Wistar rats (10 and 30 days) received three injections of BCAA pool (15.8μL/g at 1-h intervals) or saline, subcutaneously. For chronic administration, Wistar rats (7 days) received of BCAA pool or saline twice a day for 21 days, subcutaneously. Our results showed that acute administration of H-BCAA increased IL-1β (∼78%; p≤0.009) and TNF-α (∼155%; p≤0.026) levels in the cerebral cortex but not in the hippocampus of infant rats. Moreover, IL-6 levels were increased in the hippocampus (∼135%; p≤0.009) and cerebral cortex (∼417%; p≤0.008), whereas IL-10 levels were decreased only in the hippocampus (∼42%; p≤0.009). However, repeated administration of H-BCAA decreased IL-1β (∼59%; p≤0.047), IL-6 (∼70%; p≤0.009) and IFN-γ (∼70%; p≤0.008) levels in the cerebral cortex, whereas the IL-6 (∼67%; p≤0.009), IL-10 (∼58%; p≤0.01) and IFN-γ (∼67%; p≤0.009) levels were decreased in the hippocampus. These findings suggest that a better understanding of the inflammatory response in MSUD patients may be useful to develop therapeutic strategies to modulate the hyperinflammatory/hypoinflammatory axis.