title: Human cobalamin deficiency: alterations in serum tumour necrosis factor-alpha and epidermal growth factor.
abstract: OBJECTIVE
  We have previously demonstrated that vitamin B12 (cobalamin)-deficient central neuropathy in the rat is associated with local overexpression of neurotoxic tumour necrosis factor (TNF)-alpha combined with locally decreased synthesis of neurotrophic epidermal growth factor (EGF). The aims of this study were to investigate whether a similar imbalance also occurs in the serum of adult patients with clinically confirmed cobalamin deficiency and whether it can be corrected by vitamin B12 replacement therapy.
  
  
  METHODS
  We studied 34 adult patients with severe cobalamin deficiency, 12 patients with pure iron deficiency anaemia and 34 control subjects. Haematological markers of cobalamin deficiency and serum TNF-alpha and EGF levels were measured using commercial kits. Thirteen cobalamin-deficient patients were re-evaluated after 3 and 6 months of parenteral vitamin B12 treatment.
  
  
  RESULTS
  TNF-alpha was significantly higher (p < 0.01) and EGF significantly lower (p < 0.01) in the patients with cobalamin deficiency, but both were unchanged in patients with pure iron deficiency anaemia. In cobalamin-deficient patients the serum TNF-alpha levels correlated significantly with plasma total homocysteine levels (r = 0.425; p < 0.02). In the treated patients TNF-alpha and EGF levels normalised concomitantly with clinical and haematological disease remission.
  
  
  CONCLUSIONS
  In humans, as in rats, cobalamin concentration appears to be correlated with the synthesis and release of TNF-alpha and EGF in a reciprocal manner, because cobalamin deficiency is accompanied by overproduction of TNF-alpha and underproduction of EGF.
authors.affiliation: Department of Medical Sciences, Chair of Gastroenterology and Chair of Hematology, University of Milan, IRCCS Ospedale Maggiore, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Peracchi
authors.forename: F
authors.initials: F
authors.lastname: Bamonti Catena
authors.forename: M
authors.initials: M
authors.lastname: Pomati
authors.forename: M
authors.initials: M
authors.lastname: De Franceschi
authors.forename: G
authors.initials: G
authors.lastname: Scalabrino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000747:Anemia, Hypochromic / Q000145:classification; D000749:Anemia, Megaloblastic / Q000097:blood / Q000209:etiology; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D004815:Epidermal Growth Factor / Q000097:blood* / Q000172:deficiency; D005260:Female; D005492:Folic Acid / Q000097:blood; D005500:Follow-Up Studies; D005757:Gastritis, Atrophic / Q000097:blood / Q000209:etiology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007501:Iron / Q000097:blood; D000090463:Iron Deficiencies; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000209:etiology; D051381:Rats; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D014805:Vitamin B 12 / Q000627:therapeutic use; D014806:Vitamin B 12 Deficiency / Q000097:blood* / Q000150:complications / Q000188:drug therapy
chemical_list: D014409:Tumor Necrosis Factor-alpha; D006710:Homocysteine; D004815:Epidermal Growth Factor; D005492:Folic Acid; D007501:Iron; D014805:Vitamin B 12