Decreased concentrations of tumor necrosis factor-alpha in supernatants of monocytes from homozygotes for hereditary hemochromatosis.
To determine whether release of tumor necrosis factor-alpha (TNF-alpha), a cytokine that affects iron homeostasis, may be selectively altered in hereditary hemochromatosis, we measured concentrations of TNF-alpha and interleukin-1 beta (IL-1 beta) in supernatants of cultured peripheral blood monocytes from 11 homozygotes for hereditary hemochromatosis, 11 healthy individuals, and five patients with iron-loading anemia. The gene for hereditary hemochromatosis is tightly linked to the HLA locus on chromosome 6, but its exact site and product are not known. The gene for TNF-alpha also is located within the HLA region. Monocytes were incubated from 4 to 36 hours in medium alone or with added lipopolysaccharide. Mean concentrations of immunoreactive TNF-alpha in supernatants were significantly lower for subjects with hereditary hemochromatosis as compared to healthy controls (P less than .037) and patients with iron-loading anemia (P less than .005); differences between homozygotes for hemochromatosis and healthy controls were up to 4.5-fold at 4 hours (P = .008), 1.9-fold at 12 hours (P = .036), and 7.0-fold at 36 hours (P = .001). Importantly, concentrations of IL-1 beta in supernatants were not significantly different among the three groups. We conclude that release of TNF-alpha by monocytes may be selectively impaired in hereditary hemochromatosis. Deficient activity of TNF-alpha may contribute to the disordered iron metabolism of this disease.
Gordeuk
V R
VR
Department of Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44109.
Ballou
S
S
Lozanski
G
G
Brittenham
G M
GM
D000328:Adult; D002478:Cells, Cultured; D002896:Chromosomes, Human, Pair 6; D005260:Female; D005293:Ferritins / Q000378:metabolism; D006432:Hemochromatosis / Q000097:blood / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007501:Iron / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014168:Transferrin; D014409:Tumor Necrosis Factor-alpha; D005293:Ferritins; D007501:Iron