Apoptotic Leukocyte Preparation for Immune Suppression
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Solution Overview
Problem
Current methods for treating diseases characterized by pathological immune responses, such as autoimmune diseases and graft-versus-host disease, using dying leukocytes are inadequate due to the generation of pro-inflammatory mediators, leading to suboptimal efficacy and harmful side effects.
Innovation Solution
The use of dying or dead leukocytes that are substantially free of pro-inflammatory mediators like IL-1β, IL-8, and MIP1α, specifically early apoptotic monocytes isolated by substrate adherence, which are induced to undergo apoptosis through methods such as serum deprivation or steroid treatment, are used to treat diseases like graft-versus-host disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dying leukocytes are used to treat diseases with pathological immune responses, then immune suppression is achieved, but pro-inflammatory mediators are generated causing harmful side effects
Solution Approach 1:
The patent changes the physiological state parameters of leukocytes by inducing early apoptosis through specific treatments (serum deprivation, steroid treatment, UV irradiation) to alter their mediator profile from pro-inflammatory to anti-inflammatory, thereby resolving the contradiction between therapeutic efficacy and harmful side effects
Solution Approach 2:
The patent converts the typically harmful necrotic cell death pathway into a beneficial apoptotic pathway by using specific inducers (steroids, UV light) that trigger apoptosis rather than necrosis, transforming the cell death process from a source of pro-inflammatory mediators to a source of anti-inflammatory apoptotic bodies
2Productivity
If conventional cell death methods are used, then cell removal is achieved, but inflammatory reactions are induced
Solution Approach 1:
The patent replaces non-specific mechanical cell removal with a controlled biological process (apoptosis) that inherently prevents inflammation, substituting the harsh mechanical/necrotic approach with a regulated physiological mechanism that achieves cell removal without harmful inflammatory reactions
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach effectively treats diseases by suppressing immune responses without inducing inflammatory reactions, offering improved safety and effectiveness compared to prior art methods.
Implementation Method 1
A hallmark of a healthy immune system is the ability to recognize bacteria, viruses, and other foreign bodies and to effectively attack such pathogens while continuing to distinguish between the foreign bodies and the molecules, cells, tissues and organs of the body. Throughout the life span of an organism, tissues become reshaped with areas of cells being removed. This is accomplished by a process termed programmed cell death or apoptosis, the apoptotic cells disintegrating in an orderly and harmless fashion and being phagocytosed.
Data Source
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AI summary
A method of treating a disease characterized by a pathological immune response in a subject in need thereof is disclosed. The method comprises administering to the subject a therapeutically effective amount of a cell preparation which comprises dying or dead leukocytes, the dying or dead leukocytes being capable of suppressing the pathological immune response, thereby treating the disease in the subject.