Background: Chronic low-grade inflammation may be a cardinal pathophysiologic feature in the pathogenesis of frailty. Interferon-gamma (INF-γ) is an understudied proinflammatory cytokine in frailty that induces many inflammatory pathways including the guanosine triphosphate cyclohydrolase 1 (GTP-CH1) pathway. Our aim was to evaluate the GTP-CH1 pathway in Egyptian frail elderly subjects.

Methods: INF-γ, neopterin, and nitric oxide (NO) levels were measured in 80 participants.

Results: Both pre-frail and frail subjects had significantly higher levels of INF-γ, neopterin and lower levels of NO than the control group. These biomarkers were associated with the risk of frailty with significant odds ratio.

Conclusions: Elevated INF-γ levels in frail subjects may activate the GTP-CH1 pathway. Elevated neopterin and reduced NO levels correlated with an active GTP-CH1 pathway. The risk of frailty increased with elevated INF-γ and neopterin and decreased with elevated NO levels.