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Quantification of Monocyte Chemotactic Activity In Vivo and Characterization of Blood Monocyte Derived Macrophages
Published on: August 12, 2019
Reconditioned monocytes are immunomodulatory and regulate inflammatory environment in sepsis
Kshama Jain1, K Varsha Mohan1, Gargi Roy1
1National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
Abstract:
Sepsis is caused by dysregulated immune response to severe infection and hyper inflammation plays a central role in worsening the disease. The immunomodulatory properties of mesenchymal stem cells (MSCs) have been evaluated as a therapeutic candidate for sepsis. Reconditioned monocytes (RM), generated from healthy human peripheral blood mononuclear cells (PBMCs) exhibit both macrophage and MSCs-like properties. RM were administered at different stages of sepsis in a mouse model. It reduced serum levels of IL6, MCP-1, IL-10, improved hypothermia, increased survival, and recovery from 0 to 66% when combined with antibiotics in the mouse model. The reduced human leucocyte antigen DR molecules expression on RM enables their co-culture with PBMCs of sepsis patients which resulted in reduced ROS production, and up-regulated TGF-β while down-regulating IL6, IL8, and IL-10 in-vitro. RM are potentially immunomodulatory, enhance survival in sepsis mouse model and modulate inflammatory behaviour of sepsis patient's PBMCs.
Insights
Reconditioned monocytes (RM) show promise in treating sepsis by reducing inflammation and improving survival rates in mice. This novel cell therapy, derived from peripheral blood mononuclear cells (PBMCs), offers a potential new avenue for sepsis management.
Area of Science:
- Immunology
- Regenerative Medicine
- Cell Therapy
Background:
- Sepsis involves a dysregulated immune response and hyperinflammation, leading to severe illness.
- Mesenchymal stem cells (MSCs) possess immunomodulatory properties evaluated for sepsis therapy.
- Reconditioned monocytes (RM), derived from PBMCs, exhibit both macrophage and MSC-like characteristics.
Purpose of the Study:
- To evaluate the therapeutic potential of reconditioned monocytes (RM) in a preclinical sepsis model.
- To assess the immunomodulatory effects of RM in vitro using peripheral blood mononuclear cells (PBMCs) from sepsis patients.
Main Methods:
- RM were generated from healthy human PBMCs and administered at various stages in a mouse sepsis model.
- Serum cytokine levels (IL-6, MCP-1, IL-10) and survival rates were monitored.
- In vitro studies involved co-culturing RM with PBMCs from sepsis patients to analyze inflammatory markers and reactive oxygen species (ROS) production.
Main Results:
- RM administration in mice reduced serum IL-6, MCP-1, and IL-10 levels, improved hypothermia, and increased survival from 0% to 66% when combined with antibiotics.
- In vitro, RM co-culture with sepsis patient PBMCs reduced ROS production and down-regulated IL-6, IL-8, and IL-10, while up-regulating TGF-β.
- Reduced human leucocyte antigen DR expression on RM facilitated co-culture with patient PBMCs.
Conclusions:
- Reconditioned monocytes (RM) demonstrate significant immunomodulatory effects and enhance survival in a sepsis mouse model.
- RM therapy holds potential for modulating the inflammatory response in sepsis patients.
- RM represent a promising cell-based therapeutic strategy for sepsis treatment.
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