Peripheral nerve fibroblasts as a source of IL-6, TNF alpha and IL-1 and their modulation by IFN gamma

Interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), and interleu kin-1 (IL-1) are immunomodulatory cytokines produced by Schwann cells of th e peripheral nervous system (PNS). Their upregulation has been associated w ith autoimmune inflammatory diseases of the PNS such as Guillain-Barre Synd rome (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, TNF alpha and IL-1 and that the MA-1 cell line secretes thes e molecules. Flow cytometry and fluorescent activated cell sorting defined that 76% of MA-1 fibroblasts were Thy1.1(+) and 24% were Thy1.1(-). Each su bset expressed major histocompatibility class (MHC) I molecules and interce llular adhesion molecule-1 (ICAM-1). IFN gamma stimulation induced the expr ession of MHC II molecules in Thy1.1(+), but not Thy1.1(-) cells. All MA-1 cells expressed mRNA for IL-6, TNF alpha, and IL-1 plus or minus IFN gamma stimulation. IFN gamma stimulation significantly reduced the production of IL-6 but increased TNF alpha production. Direct in situ reverse-transcripta se polymerase chain reaction (RT-PCR) showed that IL-1 mRNA staining increa sed significantly following IFN gamma stimulation. These results provide ev idence 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. (C) 1998 Else vier Science B.V. All rights reserved.