Dietary n-3 fatty acids increase spleen size and postendotoxin circulating TNF in mice; role of macrophages, macrophage precursors, and colony-stimulating factor-1.
In experimental studies in mice, dietary supplementation with n-3 fatty acids (FA) alleviates inflammation and increases resistance to infection. Nevertheless, TNF production capacity was found to be increased in n-3 FA-fed mice. We previously found increased relative spleen weights in n-3 FA-fed mice. In this study, the nature of this increased spleen size was further investigated. Spleen cellularity was increased significantly in mice fed n-3 FA (fish oil 15% w/w), compared with controls fed corn oil (15%) or normal lab chow (p < 0.05). Experiments with T cell-deficient nude mice and experiments using macrophage depletion through liposomal dichloromethylene-biphosphonate revealed that the increase in spleen cellularity is T cell independent and largely due to macrophage accumulation in the spleen. Accumulation of marginal zone and red pulp macrophages was histologically and immunohistochemically confirmed. n-3 FA induced peripheral blood monocytosis and an aspecific increase in bone marrow cellularity. Postendotoxin circulating TNF concentrations were increased significantly in n-3 FA-fed mice compared with controls. Splenectomy did not abolish this increase in circulating TNF. However, after macrophage depletion through liposomal dichloromethylene-biphosphonate, circulating TNF was not detectable after endotoxin challenge. Circulating concentrations of CSF-1 did not differ between the various experimental groups. It is suggested that the cellular changes observed relate to increased constitutive production of TNF.
Blok
W L
WL
Department of General Internal Medicine, University Hospital Nijmegen, The Netherlands.
de Bruijn
M F
MF
Leenen
P J
PJ
Eling
W M
WM
van Rooijen
N
N
Stanley
E R
ER
Buurman
W A
WA
van der Meer
J W
JW
D000818:Animals; D001854:Bone Marrow Cells; D004032:Diet; D005231:Fatty Acids, Unsaturated / Q000502:physiology*; D005260:Female; D005395:Fish Oils; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013154:Spleen / Q000033:anatomy & histology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor