Effect of pyridoxine deficiency on immunological phenomena.
Measurements of serine hydroxymethyltransferase (SHMT) in resting lymphocyte cultures showed that the level of activity of this enzyme was very low. Under the influence of mitogenic stimuli serine hydroxymethyl-transferase activity was induced 5-20-fold. Addition in the cultures of 4-deoxypyridoxine, a potent antagonist of vitamin B6 coenzymes, concurrently with the mitogen, inhibits the induction of serine hydroxymethyltransferase. Thus deoxypyridoxine exerts its effects not only at the level of the enzyme itself by antagonizing the coenzyme but also at the level of its biosynthesis. Synchronous addition of vitamin B6 with deoxypyridoxine effectively reverses the inhibitory effects. The T helper cells of the lymphocyte culture are very sensitive to deoxypyridoxine action in contrast to T suppressor cells. The effect of phytohaemagglutinin or concanavalin A on the production of interleukin-1b, interleukin-2 and interleukin-2 receptors is profoundly affected by deoxypyridoxine. These results give a deeper insight of the mechanisms by which pyridoxine deficiency causes significant reduction of humoral and cellular immune responses to antigenic stimuli. On the basis of the data of this report a detailed illustration of the events that follow the T cell activation is presented. From this investigation the enzyme serine hydroxymethyltransferase emerges as a key element in the processes of immune responses and cell proliferation. Based on this finding we advance the following two propositions for possible future medical application: (i) combination of deoxypyridoxine with immunosuppressive drugs in case of immunosuppressive therapy or organ transplantation. (ii) the enzyme presents an excellent target for chemotherapy and therefore development of special agents directed against its apoprotein may prove to be a very valuable medical tool.
Trakatellis
A
A
Department of Biochemistry, Medical School, Aristotle University of Thessaloniki, Greece.
Dimitriadou
A
A
Exindari
M
M
Scountzou
J
J
Koliakos
G
G
Christodoulou
D
D
Malissiovas
N
N
Antoniadis
A
A
Polyzoni
T
T
D000917:Antibody Formation / Q000187:drug effects; D002478:Cells, Cultured; D012696:Glycine Hydroxymethyltransferase / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D011736:Pyridoxine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D026681:Vitamin B 6 Deficiency / Q000201:enzymology / Q000276:immunology*
D007375:Interleukin-1; D007376:Interleukin-2; D010835:Phytohemagglutinins; C004675:4-deoxypyridoxine; D012696:Glycine Hydroxymethyltransferase; D011736:Pyridoxine