Acylated Ghrelin Directly Modulates In Vitro Cytokine Secretion in Lipopolysaccharide-Stimulated Bone Marrow-Derived Macrophages from Male C57BL/6J Mice

Macrophages are the sentinels of the mammalian body and are involved in both inflammatory and reparative functions. Upon activation, macrophages reprogram to bias energy production and the availability of precursor molecules used to kill invading pathogens. Interrupting reprogramming has direct effects on macrophage physiology and host immunity. Macrophages express receptors for the orexigenic peptide ghrelin, and recently this stomach-derived hormone has been shown to influence inflammatory signaling. However, the underlying mechanisms are poorly understood and data available on sex differences is scarce. The objective of the current thesis is to evaluate if ghrelin pre-treatment can directly augment cytokine responses from lipopolysaccharide stimulated bone marrow-derived macrophages from male and female C57BL/6J mice in vitro. We show that pre-treating male macrophages for 4 hours with ghrelin (250 nM) prior to 24-hour stimulation with lipopolysaccharide (100 ng/mL) significantly reduces IL-1B, IL-10, and TNF-a secretion. Effect was absent in macrophages derived from females.