Addition of Glucagon to Lipid-Free Total Parenteral Nutrition Reduces Production of Prostaglandin E2 by Stimulated Splenic Macrophages

Abstract

Sepsis is a major complication of total parenteral nutrition (TPN). Impaired immunity has been suggested as being responsible for TPN-related sepsis, but it is unknown how the immune system is affected by TPN. We recently found that administration of lipid-free TPN resulted in an increase in prostaglandin Ez (PGE₂) release by stimulated splenic macrophages. This observation suggested that TPN may impair immunity through the prominent immunosuppressive effects of PGE₂. In the present study, we tested the hypothesis that addition of glucagon to TPN solution may protect against the immunosuppresive effect of TPN by modifying PGE₂ secretion. Adult, male Sprague-Dawley rats (n = 18) underwent jugular vein cannulation: group 1 (n = 7) received intravenous saline and chow ad libitum; group 2 (n = 6) received TPN (80 mL/24 h); and group 3 (n = 5) received TPN (80 mL/24 h) plus glucagon (100 μg/24 h). After 10 days, spleens were removed and splenic macrophages were isolated and cultured for 24 h in plain M199 medium (nonstimulated) or in medium containing Escherichia coli lipopolysaccharide (5 μg/mL) (stimulated). PGE ₂ release was determined by enzyme-linked immunosorbent assay. There were no differences in PGE₂ release between the groups of nonstimulated cells, but when stimulated with lipopolysaccharide, the macrophages from the TPN rats (group 2) released more PGE₂ (81.68 ± 25.99 ng/2.5 x 10⁶ cells) than the control group (16.04 ± 3.26 ng/2.5 × 106 cells). The release of PGE₂ was normalized in the TPN animals treated with glucagon (15.71 ± 3.33 ng/2.5 x 10⁶ cells). This difference was significant, with p < .05 by Tukey's test after analysis of variance. The results confirm that TPN may be immunosuppressive through the release of PGE₂ by stimulated splenic macrophages. Addition of glucagon appears to prevent this adverse effect of TPN. We hypothesize that this may take place by changes in lipid metabolism mediated by glucagon. (Journal of Parenteral and Enteral Nutrition 17:226-230, 1993)