Schwann cells produce tumor necrosis factor alpha: expression in injured and non-injured nerves

We investigated the production of tumor necrosis factor alpha, a pleotropic cytokine, in the rat sciatic nerve using immunohistochemistry for the protein and in situ hybridization for specific messenger RNA sequences. Results demonstrated that in the uninjured sciatic nerve, few endothelial cells, fibroblasts, and Schwann cells were immunoreactive for tumor necrosis factor. In situ hybridization did not yield visible results in this control tissue. Following a compression injury, the number of immunoreactive cells in the nerve fascicle was increased. In situ hybridization showed positive staining in Schwann cells and endothelial cells at seven days. These observations are the first to demonstrate the production of this proinflammatory cytokine by peripheral nerve glia, and further support other studies from this laboratory suggesting that tumor necrosis factor has a pathogenic role in nerve injury. Because this cytokine is produced by Schwann cells in intimate contact with nerve fibers, tumor necrosis factor may also have a role in the hyperalgesia associated with neuropathic pain.