Host inflammatory signaling - indirect modulation

Host inflammatory signaling - indirect modulation is a descriptive term for a therapeutic strategy rather than a specific molecular target or receptor. This approach focuses on modulating the host's internal signaling environment to control inflammation, often by targeting broad intracellular pathways such as the JAK/STAT, NF-kappaB, or MAPK cascades (Source: Nature Reviews Drug Discovery, 2020). Unlike direct inhibitors that neutralize specific cytokines, indirect modulators alter the cellular machinery responsible for producing or responding to multiple inflammatory signals simultaneously (Source: Frontiers in Immunology, 2021). This strategy is frequently employed in treating hyper-inflammatory states like sepsis or severe viral infections, such as COVID-19, where a multi-pronged reduction in the "cytokine storm" is necessary for survival (Source: The Lancet Infectious Diseases, 2021). By shifting the focus from the pathogen to the host's response, these therapies aim to prevent immune-mediated organ damage and restore homeostasis. However, the broad nature of these interventions can lead to significant safety concerns, including profound systemic immunosuppression and an increased risk of secondary infections (Source: Journal of Clinical Investigation, 2019).

Other names

Host-directed therapy (HDT)Indirect immunomodulationModulation of host inflammatory pathwaysHost response modulation

Indirect modulation involves targeting intracellular signaling cascades, transcription factors, or metabolic regulators to dampen the host's inflammatory response without directly neutralizing individual cytokines or their receptors.