Tumor necrosis factor is markedly synergistic with interleukin 1 and interferon‐γ in stimulating the production of nerve growth factor in fibroblasts

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Abstract
A possible interaction between tumor necrosis factor‐α (TNF) and other cytokines/growth factors in stimulating the production of nerve growth factor (NGF) in Swiss 3T3 cells was studied. TNF's stimulatory activity on fibroblast NGF production was synergized by interleukin‐1α (IL‐1α), IL‐1β and interferon‐γ (IFN‐γ), but was antagonized by transforming growth factor‐β (TGF‐β). The most remarkable synergistic effect was observed between TNF and IL‐1α/β; as little as 0.003 of IL‐1β markedly enhanced TNF's stimulatory activity on NGF production in the cells. These findings reinforce the idea that TNF, in concert with IL‐1α/β, plays an essential role in regulating the regeneration of peripheral nerves following injury through an indirect mechanism by which it stimulates NGF production in fibroblasts.