TRANSFORMING GROWTH-FACTOR BETA-EXPRESSION IN REACTIVE SPINAL-CORD MICROGLIA AND MENINGEAL INFLAMMATORY CELLS DURING EXPERIMENTAL ALLERGIC NEURITIS

Experimental allergic neuritis (EAN), an inflammatory demyelinating disorder of the peripheral nervous system, is preceded and accompanied by a massive microglial reaction in the spinal cord which occurs in the absence of inflammatory cells infiltrating the cord parenchyma. Since transforming growth factor beta (TGF-beta) has been shown to play a beneficial role ia experimental autoimmune disease and might be involved in the regulation of glial activity, we have investigated the expression of TGF-beta in EAN spinal cord and nerve root tissue. Adoptive transfer EAN was induced by the injection of neurotogenic T-cells specific for the P2 myelin protein. In normal spinal cord tissue, both TGF-beta1 and TGF-beta3 mRNA were constitutively expressed at low levels. Already 3 days following injection of P2-specific T-cells, TGF-beta1 mRNA levels began to increase, peaked at day 6 at levels about tenfold above normal, and thereafter declined. TGF-beta3 was induced even earlier with a sharp rise at day 3 and a peak fourfold above normal at day 4. In situ hybridization for TGF-beta1 performed on spinal cord sections 6 days after injection of cells localized TGF-beta1 mRNA to many nonneuronal cells with the typical morphology of microglia. In addition, TGF-beta1 mRNA was observed in the meninges, and massive accumulation of signal was seen over inflammatory cells infiltrating the nerve roots. Our data indicate that TGF-beta1 and -beta3 are involved in regulating the glial response in EAN and that activated microglial cells might control their own activity state by expressing TGF-beta1. The expression of TGF-beta1 by infiltrating inflammatory cells in the nerve roots might represent an important endogenous mechanism to limit the extent of inflammation. (C) 1993 Wiley-Liss, Inc.