Docosahexaenoic acid, a constituent of fetal and neonatal serum, inhibits nitric oxide production by murine macrophages stimulated by IFN gamma plus LPS, or by IFN gamma plus Listeria monocytogenes.

Murine macrophage activation is deficient in the fetus and the neonate, and in areas of the placenta perfused by the fetal circulation. Fetal and neonatal serum concentrations of docosahexaenoic acid (DHA) are 150 microM, or approximately 50-fold higher than in the adult. We previously showed that DHA inhibits activation of the gene for inducible nitric oxide synthase (iNOS) in murine macrophages stimulated in vitro with interferon gamma (IFN gamma) plus lipopolysaccharide (LPS).

Inhibition of macrophage nitric-oxide production and Ia-expression by docosahexaenoic acid, a constituent of fetal and neonatal serum.

Problem: We previously demonstrated profound inhibition of macrophage activation in the murine placenta in vivo. Given the importance of macrophages both in initiating cellular immunity by presenting antigen in the context of Ia to CD4+ T cells, and in killing cellular targets by producing nitric oxide (NO), inhibition of macrophage functions in the placenta may account for the increased susceptibility of the placenta to infection. We have also showed that docosahexaenoic acid (DHA), at concentrations present in the fetal circulation, has a major role in inhibiting macrophage Ia-expression and NO production in the placenta.

Transcription of the murine iNOS gene is inhibited by docosahexaenoic acid, a major constituent of fetal and neonatal sera as well as fish oils.

Macrophage activation is deficient in the fetus and neonate when the serum concentrations of docosahexaenoic acid (DHA) are 150 microM, or 10-50-fold higher than in the adult. We now show that DHA inhibits production of nitric oxide (NO) by macrophages stimulated in vitro by IFNgamma plus LPS, or by IFNgamma plus TNFalpha. The half-maximal inhibitory activity of DHA was approximately 25 microM.

Immunosuppressive effect of 2'-deoxycoformycin (Pentostatin) for rat islet allotransplantation.

Adenosine deaminase (ADA) is an important enzyme for proper function of lymphocytes and congenital absence of ADA results in a form of severe combined immunodeficiency syndrome. 2'-Deoxycoformycin (Pentostatin, DCF) irreversibly inhibits ADA and therefore has been suggested as an immunosuppressive drug. The present study evaluated the immunosuppressive effect of DCF for islet allotransplantation in rats.

Docosahexaenoic acid, a major constituent of fetal serum and fish oil diets, inhibits IFN gamma-induced Ia-expression by murine macrophages in vitro.

Decreased Ia expression by macrophages may account for the increased susceptibility of fetuses and neonates to infection. We chose to investigate the role of docosahexaenoic acid (DHA), an omega-3 fatty acid, on Ia expression in vitro, because neonatal serum concentrations of DHA (100-150 microM) are approximately 50 times higher than in the adult. In addition, DHA is a major component of fish-oil diets that ameliorate some autoimmune diseases and prevent renal allograft rejection.