SUMMARYMice injected with endotoxin develop endotoxaemia and endotoxin-induced death, accompanied by the oxidative burst and overproduction of inflammatory mediators. Lactoferrin, an iron binding protein, provides a natural feedback mechanism to control the development of such metabolic imbalance and protects against deleterious effects of endotoxin. We investigated the effects of intraperitoneal administration of human lactoferrin on lipopolysaccharide (LPS)-induced release of tumour necrosis factor alpha (TNF-α ), interleukin 6 (IL-6), interleukin 10 (IL-10) and nitric oxide (NO) in vivo . Lactoferrin was administered as a prophylactic, concurrent or therapeutic event relative to endotoxic shock by intravenous injection of LPS. Inflammatory mediators were measured in serum at 2, 6 and 18 h postshock induction. Administration of lactoferrin 1 h before LPS resulted in a rather uniform inhibition of all mediators; TNF by 82%, IL-6 by 43%, IL-10 by 47% at 2 h following LPS injection,and reduction in NO (80%) at 6 h post-shock. Prophylactic administration of lactoferrin at 18 h prior to LPS injection resulted in similar decreases in TNF-α (95%) and in NO (62%), but no statistical reduction in IL-6 or IL-10. Similarly, when lactoferrin was administered as a therapeutic post-induction of endotoxic shock, significant reductions were apparent in TNF-α and NO in serum, but no significant effect was seen on IL-6 and IL-10. These results suggest that the mechanism of action for lactoferrin contains a component for differential regulation of cellular immune responses during in vivo models of sepsis.

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SUMMARY1. Intestinal absorption and blood flow in anaesthetized dogs was determined after i.v. infusion of vasoactive intestinal polypeptide (VIP) (1-75-175 ng/min) to determine the contribution of the cardiovascular changes to transport.2. 22Na and 3H20 were utilized to determine the unidirectional fluxes of Na and H20 from saline perfused through the ileal lumen and the clearances of 3H20 were used to determine total and absorptive site blood flow.3. Net Na and H20 absorption were reversed to secretion by VIP at 175 ng/min due to a significant decrease in unidirectional absorptive fluxes and smaller increases in secretary fluxes.4. Arterial pressure and absorptive site blood flow were reduced in proportion to the changes in Na and H20 fluxes.5. Total and absorptive site blood flow decreased and the blood flow resistances increased.6. Prior treatment with guanethidine to suppress sympathetic effects did not greatly affect the responses to VIP. Prior treatment with atropine to suppress cholinergic effects inhibited most of the effects of VIP.7. Absorptive site blood flow was linearly related to absorptive fluxes of Na and H20 but with different slopes for results from atropinized dogs as compared to those from dogs given VIP alone or VIP plus guanethidine.8. It was concluded that VIP reduces gut absorption through a generalized cardiovascular effect and also through a mechanism which depends on the release of ACh by the gut.

To delineate the mechanism through which vasoactive compounds alter intestinal oxygen consumption and to determine the pharmacological nature of the receptors involved, we quantitated the effects of vasoconstrictors on arteriovenous oxygen difference and on vascular resistance in isolated constant-flow perfused canine small bowel. Norepinephrine (NE) and sympathetic stimulation (SS) increased vascular resistance and depressed O2 extraction. These effects were not altered by beta-blockade, but were abolished by alpha-blockade. Since capillary filtration coefficients at constant-pressure perfusion and 86Rb extraction at constant flow are reported to diminish during NE and SS, it follows that these agents reduce O2 extraction by an alpha-adrenergic closure of precapillary sphincters. Vasopressin had similar effects which were not affected by adrenergic blocking agents. Epinephrine (Epi) in high doses or after propranolol produced the same effects as NE and SS. By contrast, Epi in low doses increased O2 and 86Rb extraction. This response to low doses of Epi was not affected by phentolamine, but was reversed by propranolol. We conclude that Epi in high doses or after propranolol depresses intestinal O2 extraction by the same mechanism as NE and SS, but the mechanism through which Epi increases intestinal O2 extraction is unclear.

SUMMARY1. The unidirectional Na and H20 fluxes, vascular pressures and totaland absorptive site blood flows in the canine ileum were determined before and during I.v. saline infusion and subsequent i.v. infusion of hyperoncotic dextran. The intestinal perfusion solutions were isotonic saline or isotonic saline and mannitol, but the effects of i.v. saline or i.v. hyperoncotic dextran infusion were generally the same for both luminal solutions.2. Continuous i.v. infusion of saline caused a continuous increase in the unidirectional flux of Na and H20 into the ileal lumen, an increase in total blood flow, and an increase in venous pressure.3. The net absorption of Na and H20 was decreased by i.v. saline infusion.4. The unidirectional fluxes of Na and H20 out of the lumen, arterial pressure and absorptive site blood flow were not affected by i.v. saline infusion.5. i.v. hyperoncotic dextran infusion reversed most of the effects of saline infusion.6. The unidirectional fluxes of Na and H20 into the lumen were significantly correlated with Starling forces during I.v. saline infusion.7. It was concluded that intestinal transport of salt and water was subject to regulation by physical forces at the capillary level.