Rosiglitazone-induced Macrophage Polarization in Systemic Lupus Erythematosus: A Shift Toward Anti-inflammation

Systemic Lupus Erythematosus (SLE) is a long-term autoimmune condition resulting from a failure of immune self-regulation and skewed macrophage polarization, leading to damage to various organs. While M1 cells are the primary agents of inflammation, M2 cells are crucial for dampening the response and aiding in tissue healing. Rosiglitazone (RGZ), a PPAR-γ agonist, is widely acknowledged for its immunomodulatory effects. This study investigated the effects of RGZ on M2/M1 polarization in macrophages of SLE patients.

The study cohort included 15 female SLE patients and 10 healthy subjects. Monocytes were obtained from their peripheral blood and differentiated ex vivo to yield monocyte-derived macrophages (MDMs). We analyzed macrophage polarization through three variable types, including surface protein expression (CD163 and CD86), gene transcription levels for polarization markers, and the concentrations of key cytokines (IL-10, TGF-β1, TNF-α, IL-6, IL-1β, and IL-12).

RGZ significantly decreased CD86 and increased CD163 expression in macrophages of both normal and SLE subjects. IL-1β production was substantially suppressed in healthy subjects. However, IL-6, TNF-α, IL-12, and IL-10 levels showed non-significant differences. CD206 gene expression significantly increased in SLE patients.

RGZ enhanced the CD163/CD86 and TGF-β/TNF-α ratios in both groups, with a significant increase in SLE patients. However, the changes observed in the IL-10/IL-12 ratio were not remarkable.

RGZ induces anti-inflammatory macrophage polarization by suppressing M1 markers and boosting M2 markers in both healthy individuals and SLE patients, suggesting potential therapeutic benefits in autoimmune disease management.