Modulation of macrophage membrane phospholipids by n-3 polyunsaturated fatty acids increases interleukin 1 release and prevents suppression of cellular immunity following hemorrhagic shock
W. Ertel, M. H. Morrison, A. Ayala and I. H. Chaudry
Department of Surgery, Michigan State University, East Lansing 48824-1315.
Studies have suggested that the significant suppression of cellular
immunity following hemorrhage may be due to an increased release of
prostaglandin E2 (PGE2) by macrophages. Since diets high in n-3
polyunsaturated fatty acids decrease PGE2 synthesis, we assessed whether
hemorrhage-induced immunosuppression could be prevented by dietary
manipulation. C3H/HeN mice were fed for 3 weeks with fat sources derived
from corn oil, safflower oil, or fish oil, then bled to a mean blood
pressure of 35 mm Hg maintained for 60 minutes. Following this, the animals
were adequately resuscitated with fluids and killed 24 hours later. In the
corn oil and safflower oil groups, hemorrhage resulted in a significant
increase in PGE2 release by peritoneal macrophages, a marked suppression of
peritoneal macrophage antigen presentation capacity, interleukin 1 release,
splenocyte proliferation, and interleukin 2 secretion compared with shams.
However, feeding mice with fish oil for 3 weeks prior to hemorrhage
prevented the rise in PGE2 release and maintained normal macrophage and
splenocyte functions following hemorrhage. Thus, the elevated release of
PGE2 by peritoneal macrophages plays a pivotal role in hemorrhage-induced
immunosuppression. Moreover, diets high in n-3 polyunsaturated fatty acids
may offer a new therapeutic approach for preventing posthemorrhage
immunosuppression and increased mortality from sepsis.
