Type I Interferon Inhibitors for Monocytopoiesis Modulation
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Solution Overview
Problem
Current methods fail to effectively modulate monocytopoiesis, leading to excessive inflammatory cell accumulation in diseases like atherosclerosis and sepsis, where type I interferons play a dual role in both resolving infections and causing septic shock, making their exact role in sepsis unclear.
Innovation Solution
Administering a therapeutically effective amount of an inhibitor of type I interferons to reduce monocytopoiesis, particularly suitable for treating monocyte-dependent inflammatory disorders and sepsis, by promoting the differentiation of monocyte-derived phagocytes and reducing inflammatory cell accumulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If type I interferons are administered to resolve infections, then infection resolution is improved, but septic shock and inflammatory cell accumulation worsen
Solution Approach 1:
The patent uses a selective inhibitor of type I interferon signaling as an intermediary substance that blocks the harmful effects of type I interferons on monocytopoiesis while allowing the administration of type I interferons for infection resolution. This intermediary selectively interferes with the signaling pathway to prevent septic shock and inflammatory cell accumulation without completely abolishing the anti-infective effects.
Solution Approach 2:
The patent extracts and selectively inhibits the harmful signaling pathway of type I interferons that leads to excessive monocytopoiesis and septic shock, while preserving the beneficial anti-infective effects. By taking out the specific harmful signaling component through selective inhibition, the therapy can resolve infections without causing septic shock.
2Reliability
If monocytopoiesis is allowed to proceed normally, then infection control is improved, but inflammatory cell accumulation and disease aggravation worsen
Solution Approach 1:
The patent introduces a feedback mechanism by administering selective type I interferon signaling inhibitors that respond to the presence of excessive inflammatory cells or signs of septic shock. The inhibitor modulates monocytopoiesis in real-time, reducing inflammatory cell accumulation when it becomes excessive while allowing normal monocytopoiesis to proceed for infection control under normal conditions.
3Object-affected harmful factors
If type I interferon signaling is completely inhibited, then septic shock is prevented, but infection resolution capability is reduced
Solution Approach 1:
The patent changes the parameter of type I interferon signaling from complete activation to selective modulation. By using selective inhibitors that target specific downstream components of the type I interferon pathway rather than blocking the receptor completely, the therapy maintains sufficient signaling for infection resolution while preventing the harmful threshold that leads to septic shock and excessive monocytopoiesis.
Data Source
AI summary
Monocytopoiesis is a hematological process that supplies the periphery with monocytes and subsequently with macrophages and monocyte-derived dendritic cells. Typically, monocytes circulate in the bloodstream for a very short time before undergoing apoptosis, however, stimulatory signals can trigger monocyte survival by inhibiting the apoptotic pathway, and thus contribute to the maintenance of the inflammatory response. Accordingly, there is a need for methods and pharmaceutical compositions for modulating monocytopoiesis. Now, the inventors show that type I interferons signaling promote the differentiation of monocyte-derived phagocytes at the level of their progenitors. Importantly, IFN-alpha and -beta were found to efficiently generate the development of monocyte-derived antigen-presenting cells while having no impact on the precursor activity of conventional dendritic cells. Accordingly, modulators of type I interferon (e.g. neutralizing antibodies or type I IFN polypeptides) would be suitable for modulating monocytopoiesis in subjects in need thereof.