Abstract
Background: It has been proposed that Hyaluronan (HA) acts as a vehicle for cytokines due to the strong negative charge on its surface. We hypothsized that HA would function like a cytokine scavenger, reducing inflammatory signaling cascade leading to improved survival in endotoxemia.
Methods: Endotoxin (Salmonella, 10 mg/kg) or an equal amount of 0.9% NaCl (NS) was injected into the jugular vein of rats. HA (1600 kDa, 0.35%) or NS was given 0.5 ml/h for 3 h. HA or NS infusion was started at three different time points; 30 min before, 1 hour after, and 4 hour after endotoxin injection. Rats were divided into control and HA groups at three different time point.
Results: The survival rate (%) of rats treated with HA was higher (90%) than in controls' (60%) treated with NS infusion 30 min before LPS injection; HA was higher (90%) than in controls' (50%) when HA or NS infused 1 h after LPS; HA was higher (60%) than in controls' (20%), when HA or NS infused 4 h after LPS. Bronchoalveolar lavage (BAL) of the animals surviving HA or NS infusion 4 h after LPS showed that total cell count and neutrophils were significantly (p < 0.01) reduced in the HA treated groups compared to controls (total cell count, 9.2×104/ml vs. 61×104/ml; neutrophils, 21×104/ml vs. 0.2×104/ml, respectively). Serum cytokines of the animals surviving HA or NS infusion 4 h after LPS showed that TNF-alpha and MIP-2 were significantly (p < 0.01) lower in the HA treated groups compared to controls (70.7 vs. 120.3 pg/ml; 1506 vs. 3459 pg/ml, respectively).
Conclusion: Continuous infusion of hyaluronan, 1600 kDa, reduced BAL cell count and serum cytokines, and improved survival in the endotoxemic rats.
- © 2011 ERS