Human cobalamin deficiency: alterations in serum tumour necrosis factor-alpha and epidermal growth factor

Objectives: We have previously demonstrated that vitamin B-12 (cobalamin)-d eficient central neuropathy in the rat is associated with local overexpress ion 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 unbalance also occurs in the serum of adult patients with clinically confirmed cobalamin deficien cy and whether it can be corrected by vitamin B-12 replacement therapy. Pat ients and methods: We studied 34 adult patients with severe cobalamin defic iency, 12 patients with pure iron deficiency anaemia and 34 control subject s. Haematological markers of cobalamin deficiency and serum TNF-alpha and E GF levels were measured using commercial kits. Thirteen cobalamin-deficient patients were re-evaluated after 3 and 6 months of parenteral vitamin B-12 treatment. Results: TNF-alpha was significantly higher (p < 0.01) and EGF significantly lower (p < 0.01) in the patients with cobalamin deficiency, b ut both were unchanged in patients with pure iron deficiency anaemia. in co balamin-deficient patients the serum TNF-alpha. levels correlated significa ntly with plasma total homocysteine levels (r = 0.425; p < 0.02). In the tr eated patients TNF-<alpha> and EGF levels normalised concomitantly with cli nical and haematological disease remission. Conclusions: In humans, as in r ats, cobalamin concentration appears to be correlated with the synthesis an d release of TNF-alpha and EGF in a reciprocal manner, because cobalamin de ficiency is accompanied by overproduction of TNF-alpha and underproduction of EGF.