Opioide in der Schmerzkontrolle durch M2 Makrophagen und M2 Mikroglia
Zusammenfassung der Projektergebnisse
IL-4 is an anti-inflammatory cytokine, which can be protective in inflammatory and neurologic disorders, and can alleviate pain. The beneficial actions of IL-4 are thought to result from decreasing the activity of inflammatory mediators, such as proinflammatory cytokines. In this project we demonstrated that, (a) IL-4 injection can reduce pain responses in an animal model via release of opioid peptides from immune cells (M1 macrophages) at injured nerves and (b) repeated IL-4 treatment induces M2 macrophages to continuously produce opioid peptides and ameliorate pain. As a model of neuropathic pain, we used chronic constriction injury (CCI) of the sciatic nerve in male mice. Injured nerves were predominately infiltrated by proinflammatory M1 macrophages and IL-4 did not change their numbers or phenotype. These macrophages secreted opioid peptides after mobilization of calcium from intracellular stores. When IL-4 was applied repeatedly, antiinflammatory M2 macrophages synthesized opioid peptides continuously. These effects were accompanied by a long-lasting attenuation of neuropathy-induced mechanical pain responses. Fostering such opioid-mediated actions of macrophages may be a strategy to tackle pathological pain without eliciting adverse central side effects such as apnea or addiction.
Projektbezogene Publikationen (Auswahl)
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IL-4 induces M2 macrophages to produce sustained analgesia via opioids. JCI Insight 2020, 27;5(4):e133093
Celik MÖ, Labuz D, Keye J, Glauben R, Machelska H
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Immune cell-mediated opioid analgesia. Immunol Lett 2020, 227:48-59
Celik MÖ, Machelska H
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Opioid Receptors in Immune and Glial Cells-Implications for Pain Control. Front Immunol 2020, 4;11:300
Celik MÖ, Machelska H
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Interleukin-4 Induces the Release of Opioid Peptides from M1 Macrophages in Pathological Pain. J Neurosci 2021, 31;41(13):2870-2882
Labuz D, Celik MÖ, Seitz V, Machelska H
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Real-Time Quantitative Reverse Transcription PCR for Detection of Opioid Receptors in Immune Cells. Opioid Receptors 2021, 83-95
Celik MÖ, Labuz D, Machelska H
