Reticuloendothelial system and lymphatic system (RES/LS)

The reticuloendothelial system (RES), now more accurately termed the mononuclear phagocyte system (MPS), and the lymphatic system are integrated physiological networks essential for immune defense, waste removal, and fluid balance. The RES is primarily composed of phagocytic cells, such as macrophages and monocytes, located in the spleen, liver (Kupffer cells), and bone marrow, which function to filter the blood and remove aged cells or pathogens [1]. The lymphatic system consists of a network of vessels, nodes, and organs like the thymus and spleen that transport lymph and facilitate the maturation and circulation of immune cells [2]. In a pharmacological context, these systems are not considered single molecular targets; however, they play a critical role in the pharmacokinetics and biodistribution of large molecules, liposomes, and nanoparticles, which are frequently sequestered by the RES [3]. Pathological conditions associated with these systems include lymphomas, lymphedema, and the systemic spread of infections or metastatic cancer cells [4]. Understanding the interaction between therapeutic agents and these systems is vital for optimizing drug delivery and minimizing off-target immune activation [3]. Sources: [1] StatPearls, Mononuclear Phagocyte System (https://www.ncbi.nlm.nih.gov/books/NBK551651/) [2] National Cancer Institute, Lymphatic System (https://www.cancer.gov/publications/dictionaries/cancer-terms/def/lymphatic-system) [3] Nature Nanotechnology, The mononuclear phagocyte system in drug delivery (https://www.nature.com/articles/s41565-017-0029-2) [4] Britannica, Reticuloendothelial system (https://www.britannica.com/science/reticuloendothelial-system)

Other names

Mononuclear phagocyte systemMPSLymphoid systemMacrophage systemReticulohistiocytic system

Drugs do not target these systems as a single molecule; instead, they utilize these systems for distribution (e.g., nanoparticle uptake by macrophages) or target specific cellular subsets like B-cells or T-cells within the lymphoid tissues.