Role of nonspecific myelin destruction by delayed type hypersensitivity in primary demyelination

Abstract

To clarify the role of nonspecific myelin destruction mediated by delayed type hypersensitivity (DTH) in primary demyelination, DTH to tuberculin was induced within the endoneurium by intraneural injection of purified protein derivative (PPD) or sonicated Mycobacterium tuberculosis into the sciatic nerves of Lewis rats and guinea pigs which had previously been sensitized to tuberculin. The morphological features of the nerves proximal to the site of needle insertion were assessed 5 days after injection. By changing the PPD concentration of solution for intraneural injection, various degrees of DTH reaction could be produced in the nerve. Infiltration of mononuclear cells including macrophages was observed around the vessels and in the vicinity of the myelin sheaths. Although nonspecific damage of axons, myelin sheaths and Schwann cells was observed in areas heavily infiltrated with inflammatory cells, primary demyelination was hardly recognized. Another group of Lewis rats previously immunized with galactocerebroside (GC), the major glycolipid hapten of myelin, in Freund's complete adjuvant received intraneural injection of PPD or GC liposomes. Neither cellular nor humoral immunity to GC was detected in these rats. The nerves injected with GC liposomes showed no inflammatory cell infiltration except for a few macrophages containing liposomes and those injected with PPD showed infiltration of mononuclear cells without primary demyelination. Our findings reveal that nonspecific myelin destruction induced by DTH does not play an important role in immune-mediated demyelination.