Combination of Glutamine and Ulinastatin Treatments Greatly Improves Sepsis Outcomes

BACKGROUND: Sepsis is one of the most dangerous syndromes, has extremely high mortality, and is caused by the body’s extreme responses to an infection. The pathogenesis of sepsis is very complex and remains largely unknown and thus the treatments for sepsis are limited. Here, we evaluated the treatment results of two potential drugs, glutamine and ulinastatin, on sepsis. METHODS: CLP rat model was used to study sepsis. Gastrostomy was performed to deliver the drugs. Flow cytometry was employed to measure CD4 and CD8 levels. May–Grünwald–Giemsa staining was used to count the numbers of monocytes and neutrophils in the blood. ELISA assay was performed to assess the levels of PCT, IL-6, TNFα, and IL-1β. RESULTS: Sepsis was successfully induced with the standard CLP rat model. Both glutamine and ulinastatin treatments greatly improved the outcomes of sepsis, but the combination of both treatments had the maximum therapeutic effect. Mechanistically, PCT, IL-6, TNFα, and IL-1β levels were significantly diminished following glutamine and ulinastatin treatments, suggesting an inhibition of inflammatory responses. Further, CD4 and CD4/CD8 ratio, and the numbers of monocytes and neutrophils were greatly up-regulated by glutamine and ulinastatin, indicating an enhanced immunity. CONCLUSION: Glutamine and ulinastatin treatments largely mitigate sepsis shock by suppressing the inflammatory responses of the body and strengthening the immune system. Combination of these two drugs could serve as a potential treatment for sepsis.