Growth hormone restrains inflammatory activity of microglia/macrophages in CNS autoimmunity.

Abstract

Growth hormone (GH) has been implicated in immune regulation, but its effects on microglia/macrophages during neuroinflammation remain insufficiently characterized. Here, we investigated the impact of GH on microglia/macrophages activation using complementary in vitro and in vivo approaches. In LPS-stimulated BV2 microglia, GH induced anti-inflammatory and antioxidant responses, accompanied by morphological features consistent with reduced cellular activation. In vivo, GH administration in rats with experimental autoimmune encephalomyelitis (EAE) delayed disease onset and significantly reduced disease duration, severity, and cumulative clinical score. GH also affected peripheral immune responses, as evidenced by decreased production of the pro-inflammatory cytokines interferon-γ and interleukin-17 by lymph node cells draining the site of the immunization. However, the major effect of GH was observed in the central nervous system, where GH profoundly altered the inflammatory amoeboid morphology of microglia/macrophages typically observed at the EAE peak. Quantitative morphometric, skeleton, and fractal analyses of microglia/macrophages demonstrated reduced process complexity, decreased cell area and perimeter, increased circularity and solidity, reduced fractal dimension and lacunarity, and diminished branching parameters, accompanied by increased iNOS expression at the EAE peak. GH treatment prevented these changes, restoring microglia/macrophages morphological complexity and attenuating pro-inflammatory features. Collectively, these findings indicate that GH modulates neuroinflammatory responses by regulating the microglia/macrophages activation state, supporting a more ramified, surveillant microglia/macrophages phenotype. This positions GH as a disease phase-sensitive regulator of neuroinflammatory processes relevant to autoimmune disorders of the central nervous system.