Peripheral nerve fibroblasts as a source of IL-6, TNFalpha and IL-1 and their modulation by IFNgamma.

Interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interleukin-1 (IL-1) are immunomodulatory cytokines produced by Schwann cells of the peripheral nervous system (PNS). Their upregulation has been associated with autoimmune inflammatory diseases of the PNS such as Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Neuropathy (CIDP). We now report that PNS fibroblasts and a PNS fibroblast cell line - MA-1 express mRNA for IL-6, TNFalpha and IL-I and that the MA-1 cell line secretes these molecules. Flow cytometry and fluorescent activated cell sorting defined that 76% of MA-1 fibroblasts were Thy1.1+ and 24% were Thy1.1-. Each subset expressed major histocompatibility class (MHC) I molecules and intercellular adhesion molecule-1 (ICAM-1). IFNgamma stimulation induced the expression of MHC II molecules in Thy1.1+, but not Thy1.1(-) cells. All MA-1 cells expressed mRNA for IL-6, TNFalpha, and IL-1 plus or minus IFNgamma stimulation. IFNgamma stimulation significantly reduced the production of IL-6 but increased TNFalpha production. Direct in situ reverse-transcriptase polymerase chain reaction (RT-PCR) showed that IL-1 mRNA staining increased significantly following IFNgamma stimulation. These results provide evidence for the first time that not only Schwann cells, but also peripheral nerve fibroblasts are a source of immunomodulatory cytokines within the PNS and may contribute to inflammatory processes in PNS disease.