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 E2 (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 immunosuppressive 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). PGE2 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 x 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.
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Nutrition and Dietetics