Search

The administration of insulin is recommended to patients with severe sepsis and hyperglycemia. Previously, we demonstrated that insulin may have direct anti- inflammatory properties and counteracted fluid losses from the circulation by normalizing the interstitial fluid pressure (PIF). PIF is one of the Starling forces determining fluid flux over the capillary wall, and a lowered PIF is one of the driving forces in early edema formation in inflammatory reactions. Here we demonstrate that insulin restores a lipopolysaccharide (LPS)-lowered P1~ via a mechanism involving integrin ~ In C57 black mice (n = 6), LPS lowered PIF from -0.2 ± 0.2 to -1.6 ± 0.3 (P < 0.05) and after insulin averaged -0.8 ± 0.2 mmHg (P = 0.098 compared with after LPS). Corre- sponding values in wild-type BALB/c mice (n = 5) were -0.8 ± 0.1, - 2.1 ± 0.3 (P < 0.05), and -0.8 ± 0.3 mmHg (P < 0.05 compared with LPS) after insulin administration~ In BALB/c integrin f33- deficient (13) mice (n = 6), LPS lowered PIF from -0.1 ± 0.2 to -1.5 ± 0.3 mmHg (P < 0.05). Insulin did not, however, restore PIF in these mice (averaged -1.7 ± 0.3 mmHg after insulinadministra- tion). Cell-mediated collagen gel contraction can serve as an in vitro model for in vivo measurements of PIF. Insulin induced crV~3-integrin- dependent collagen gel contraction mediated by C2C12 cells. Our findings suggest a beneficiary effect of insulin for patients with sepsis with regard to the fluid balance, and this effect may in part be due to a normalization of PIF by a mechanism involving the integrin aV133. [ABSTRACT FROM AUTHOR]