| First Author | Adi S | Year | 1992 |
| Journal | J Clin Invest | Volume | 89 |
| Issue | 5 | Pages | 1603-9 |
| PubMed ID | 1569198 | Mgi Jnum | J:1123 |
| Mgi Id | MGI:49655 | Doi | 10.1172/JCI115755 |
| Citation | Adi S, et al. (1992) Role for monokines in the metabolic effects of endotoxin. Interferon-gamma restores responsiveness of C3H/HeJ mice in vivo. J Clin Invest 89(5):1603-9 |
| abstractText | To examine the role of cytokines in mediating the lipogenic effects of endotoxin (LPS), we studied the effects of LPS and cytokines on hepatic fatty acid synthesis in LPS-sensitive C3H/OuJ mice and in LPS-resistant C3H/HeJ mice, whose macrophages are defective in the ability to produce tumor necrosis factor (TNF) and IL-1 in response to LPS. HeJ mice were 16-fold less sensitive than OuJ mice to the lipogenic effect of LPS. In OuJ mice, 10 micrograms of LPS caused a maximal increase in hepatic lipogenesis (3.86 +/- 0.41-fold), whereas in HeJ mice the maximal increase was only 1.79 +/- 0.32-fold after 100 micrograms of LPS. This lipogenic response paralleled the decreased ability of LPS to increase hepatic and splenic levels of mRNAs for TNF and IL-1 and serum levels of TNF in HeJ mice. In contrast, the maximal effect of TNF on lipogenesis was greater and the sensitivity to TNF was increased 2.4-fold in HeJ mice compared to OuJ mice. Administration of IFN-gamma before LPS in HeJ mice had no effect on IL-1 mRNA, but partially restored the LPS-induced increase in hepatic and splenic mRNA for TNF and serum TNF levels, which may account for the partial restoration of sensitivity to the lipogenic effect of LPS after IFN-gamma treatment. These results indicate that cytokines produced by mononuclear leukocytes mediate the lipogenic effects of LPS. |
