Estrogen restores cellular immunity in injured male mice via suppression of interleukin-6 production.

This study examined whether estrogen treatment can improve immunity in male mice after combined ethanol and burn injuries. 17beta-Estradiol [estrogen, given subcutaneously (s.c.)] or oil (control) was administered at 30 min and 24 h postinjury. At 48 h postinjury, ethanol/burn-injured mice demonstrated significant suppression of cellular immunity. Estrogen treatment restored the delayed-type hypersensitivity (P<0.01) and splenocyte-proliferative (P<0.05) responses, reduced macrophage interleukin-6 (IL-6) (P<0.05), and increased survival after bacterial challenge (P<0.01). In vitro neutralization of IL-6, combined with macrophage supernatant experiments, confirmed that the beneficial effects of estrogen treatment were mediated through modulation of macrophage IL-6 production. Moreover, estrogen treatment resulted in a decrease in splenic nuclear factor-kappaB (NF-kappaB) activation in injured mice. There were no changes in cellular NF-kappaB or IkappaBalpha protein expression or IkappaBalpha phosphorylation at serine 32. Taken together, these studies suggest that estrogen treatment of injured male mice improves cellular immunity through direct modulation of NF-kappaB activation.

Development of a low flow resistance intravenous oxygenator.

A potentially attractive support device for patients with acute respiratory failure is an intravenous membrane oxygenator. One problem, however, is that the membrane surface area required for sufficient gas exchange can unduly increase vena caval pressure drop and impede venous return. The purpose of this study was to design and develop an intravenous oxygenator that would offer minimal venous flow resistance in situ. The device uses a constrained fiber bundle of smaller cross sectional size than the vena cava so as to effect an intentional shunt flow of venous blood around the fiber bundle and reduce the venous pressure drop caused by the device. A pulsating balloon within the fiber bundle redirects part of this shunt flow into reciprocating flow in and out of the fiber bundle. This offers dual advantages: 1) Blood flow through the fiber bundle is mainly perpendicular to the fibers; and 2) the requisite energy for driving flow comes largely from the pneumatic system pulsating the balloon, not from a venous pressure drop. In this mode a full length device with a 2 cm fiber bundle in a 2.5 cm blood vessel would offer a pressure drop of only a few millimeters of mercury. The use of constrained fiber bundles requires good uniformity of fiber spacing for effective gas exchange. Several prototypes have been fabricated, and CO2 and O2 exchange rates of up to 402 and 347 ml/min/m2 have been achieved during acute animal implantation.