Ghrelin Prevents TNF-α-induced Systemic Inflammation During LPS-mediated toxicity
Allexan, Sarah Sonya
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Sepsis, a homeostatic upset of the immune response resulting from infection, is the ninth leading cause of death in the United States. Sepsis involves overproduction of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) which damage tissue. This damage often leads to systemic inflammatory response syndrome (SIRS) and multiple organ failure. Recently, ghrelin, a stomach-derived peptide has been discovered to possess potent anti-inflammatory effects in response to overproduction of proinflammatory cytokines. In this study, mice were injected with lipopolysaccharide (LPS) to induce sepsis and determine the systemic and hepatic effects of exogenous ghrelin. We hypothesize that ghrelin reduces inflammation following sepsis by a mitogen activated protein kinase (MAPK) and TNF-α mediated mechanism. To determine if ghrelin inhibited TNF-α and proinflammatory cytokine Interleukin-1α (IL-1α) accumulation, we quantified concentrations of TNF-α and IL-1α using an enzyme-linked immunosorbent assay (ELISA). We performed Western blots for phosphorylated-p38 MAP kinase (PO4-p38 MAPK) to determine if ghrelin influenced levels of PO4-p38 MAPK following sepsis. Ghrelin decreased TNF-α concentrations in blood serum, however it did not significantly affect serum concentrations of IL-1α. Contrary to our hypothesis, increased concentrations of PO4-p38 MAPK were seen in ghrelin-treated mice. Our study confirms ghrelin’s anti-inflammatory effects in preventing pro-inflammatory cytokine production, however, initiates inquiry into ghrelin’s effects on the MAPK pathway. Ghrelin treatment may be a viable therapeutic for critical care patients suffering from sepsis reducing the severity of the systemic immune response thereby conferring overall improvement from tissue damage and lethal outcomes.