DIFFERENTIAL CYTOKINE PRODUCTION IN CLONAL MACROPHAGE AND T-CELL LINES CULTURED WITH BIFIDOBACTERIA

When used in commercial fermented dairy products, bifidobacteria may e nhance immunity by stimulating cytokine secretion by leukocytes. To as sess whether interaction between bifidobacteria and leukocytes promote cytokine production, we cultured RAW 264.7 cells (macrophage model) a nd EL-4.IL-2 thymoma cells (helper T-cell model) in the presence of 14 representative strains of heat-killed bifidobacteria. In unstimulated RAW 264.7 cells, all bifidobacteria induced pronounced increases (up to several hundred-fold) in the production of tumor necrosis factor-al pha compared with that of controls. Interleukin-6 production by unstim ulated cells also increased significantly, but less than did tumor nec rosis factor-alpha. Upon concurrent stimulation of RAW 264.7 cells wit h lipopolysaccharide, production of tumor necrosis factor-alpha and in terleukin-6 were both enhanced between 1.5- to 5.8-fold and 4.7- to 7. 9-fold, respectively, when cultured with 10(8) bifidobacteria/ml. In u nstimulated EL-4.IL-2 cells, bifidobacteria had no effect on the produ ction of interleukin-2 or interleukin-5. Upon stimulation of EL-4.IL-2 with phorbol-12-myristate-13-acetate, there were variable increases i n interleukin-2 secretion (up to 2.4-fold for 10(6) Bifidobacterium Bf -1/ml) and interleukin-5 secretion (up to 4.6-fold for 10(8) B. adoles centis M101-4). The results indicated that, even when variations among strains were considered, direct interaction of most bifidobacteria wi th macrophages enhanced cytokine production, but the effects on cytoki ne production by the T-cell model were less marked. Interestingly, the 4 bifidobacteria strains used commercially for dairy foods showed the greatest capacity for cytokine stimulation. The in vitro approaches e mployed here should be useful in future characterization of the effect s of bifidobacteria on gastrointestinal and systemic immunity.