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M1-and M2-Like Macrophages-Centered Therapies in S Lupus E. 2021

pattismith

Senior Member
Messages
3,940
Frontiers | Macrophage Polarization and Plasticity in Systemic Lupus Erythematosus (frontiersin.org) 2021
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Another compound that has been experimentally used to control SLE is pioglitazone.
Pioglitazone corresponds to a peroxisome proliferator-activated receptor (PPAR)-γ agonist that is widely used to treat diabetes.
In addition to its anti-diabetic effect, this drug also has anti-inflammatory properties (118).
Such anti-inflammatory effect has been reported to benefit inflammatory diseases, including SLE.
Indeed, an ex vivo study of newly diagnosed lupus patients showed that activation of PPAR-γ by pioglitazone could induce anti-inflammatory properties by promoting the expression of M2-like macrophages and decreasing the expression of M1-like macrophage (119).
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Clinically, Virgin olive oil (VOO) has been successfully used to ease symptoms in patients with lupus. A study conducted in humans proved that the phenolic fraction of extra virgin oil provided a beneficial effect on immune-inflammatory diseases such as SLE (121). Although this particular article does not state that this immunoregulation is achieved by macrophages, a more recent study has revealed that VOO dampens TLR4, which plays a role in both macrophage activation and polarization (122).
Moreover, a comparison of the use of virgin olive oil and sunflower oil in murine lupus showed that the former could block the expression of M1 subtype macrophage while enhancing the M2 phenotype (122). ...

Clinically, azithromycin, a macrolide antibiotic useful for controlling inflammation in various diseases (134), has been proven to ease lupus flare via the regulation of M2-like macrophages. In vivo and in vitro studies in SLE patients revealed that azithromycin promotes M2 polarization via the pl3k/Akt pathway, resulting in the suppression of inflammation and SLE remission (135). Albeit its reported side effects (136), azithromycin does have a good record of safety, and exploring it could offer a new therapeutic strategy for lupus patients. Another drug that favors the M2 phenotype is steroid.

A picture from Phenotype change of polarized microglia after intracerebral hemorrhage: Advances in research - ScienceDirect



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pattismith

Senior Member
Messages
3,940
Interestingly Pioglitazone and Azithromycin seems to have different type of action on this 2019 study
Sexual Dimorphism of Pain Control: Analgesic Effects of Pioglitazone and Azithromycin in Chronic Spinal Cord Injury | Journal of Neurotrauma (liebertpub.com)

Three months after SCI, mice were treated with PIO (10 mg/kg, intraperitoneal) or AZM (160 mg/kg, oral). We observed a sex-specific effect of PIO with significant antihyperalgesic effects in females, but not males.

In contrast, AZM was effective in both sexes.

Our data support the use of PIO and AZM as novel therapies for SCI pain and highlight the importance of considering sex as a biological variable in clinical and experimental SCI pain research.
 
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