Lactoferrin moderates LPS-induced hypotensive response and gut injury in rats

Hypotension is a physiologic state of low blood pressure, the causes of which range from dehydration to underlying serious medical disorders. The aim of this study was to assess the utility of lactoferrin (LF), a natural immunomodulator, to restrain LPS-induced hypotension in rats. LF has previously demonstrated a role in mediation of immune responses, including control of inflammatory cytokine production during acute inflammation. Rats were administered with LF by gavage at 1h or 18h prior to LPS injections. Heart rate (HR) and mean arterial blood pressure (MAP) were continuously recorded post LPS administration for 6h. Simultaneously to hemodynamic measurements, serum was examined for TNF-α, IL-6, and TGF-β production. At termination, the proximal duodenum was subjected to histopathological analysis. LF administered at 1h prior to LPS protected rats from the LPS-induced hypotension. The protective effect on MAP was also apparent when LF was administered as a pretreatment 18h prior to LPS challenge, although the effect was lessened. For all groups, LF pretreatment led to a minor, but insignificant, improvement in HR post LPS administration. In addition, when rats were given LF 1h before LPS, they showed a significant decrease in serum TNF-α and IL-6 production. LF did not affect the production level of serum TGF-β. Of high importance, LF was able to confer histo-pathological protection of intestinal tissue post LPS administration, for both the 1h and 18h LF pretreatment groups. These studies indicate a potential for clinical utility of LF to control hypotension. ► Lactoferrin (LF) was examined to prevent septic events in a LPS-induced hypotension model in rats. ► LF Administration prior to LPS challenge enabled reduced mean arterial pressure (MAP) and reduced hypotensive response. ► Concurrent with reduction in MAP, LF administration allowed homeostasis of serum TNF-α and IL-6, but not TGF-β. ► LF demonstrated protection of proximal duodenal architectural integrity due to hypotensive changes.