Morphine's role in macrophage polarization: Exploring M1 and M2 dynamics and disease susceptibility

• Published in: Journal of neuroimmunology Vol. 400; p. 578534
• Main Authors: Malik, Jonaid Ahmad, Agrewala, Javed N.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.03.2025
• Subjects: Analgesics, Opioid - pharmacology; Animals; Cell Polarity - drug effects; Disease Susceptibility - immunology; Humans; Macrophage Activation - drug effects; Macrophage Activation - immunology; Macrophages - drug effects; Macrophages - immunology; Morphine - pharmacology; Morphine, M1 and M2 macrophages, opioids, substance of abuse, drug dependency; Opioid-Related Disorders - immunology; NF-κB; AMPA; NLRX1; SOA; MMPs; GABA; NMDA; Morphine, M1 and M2 macrophages, opioids, substance of abuse, drug dependency; MAPK; ERK; OUD
• ISSN: 0165-5728; 1872-8421; 1872-8421
• DOI: 10.1016/j.jneuroim.2025.578534

Morphine is a globally prevalent substance of misuse, renowned for its immunosuppressive effects mediated through opioid receptors expressed on immune cells. Macrophages are crucial antigen-presenting cells that fulfill diverse roles, such as antigen presentation, phagocytosis, wound healing, and disease protection. They are typically classified based on their activation states: M1 (proinflammatory), M2 (anti-inflammatory), and M0 (resting). Morphine significantly modulates immune responses and neuroinflammation, further complicating the landscape of opioid dependency and disease susceptibility. The association of macrophages under the influence of morphine needs to be understood under various diseased conditions. Several studies have been focused on investigating the impact of morphine on macrophage function and its implications in infectious diseases and brain-associated diseases. To light this subject, we have discussed recent advancements in understanding the influences between morphine, macrophage function, polarization, infection, brain tumors, and drug dependency. This article explores the complex relationship between morphine, macrophages, and related pathologies. Consequently, discussing deeper insights into these dynamics could guide effective treatments for substance abuse disorders. •Morphine modulates the function and differentiation of macrophages.•Morphine significantly modulates neuroinflammation and disease susceptibility.•Morphine polarizes the macrophages to the tumor-associated M2 phenotype in the brain.•Morphine augments HIV and SIV persistence in the CNS.•Morphine induces adaptive changes in brain receptors, neuronal circuits, and neurotransmitters.