Role of complement in demyelination in vitro by multiple sclerosis serum and other neurological disease sera

Multiple sclerosis (MS) sera can demyelinate and cause selective cellular changes to organ cultures of rodent CNS which suggests possible immunoglobulin involvement. The complement dependence of this serum action was investigated using complement-inactivating agents and radiolabelled rat cerebellar cultures. After heat inactivation at 56 degrees C, the in vitro effects of MS, chronic relapsing experimental allergic encephalomyelitis (cr-EAE) and Guillain-Barré syndrome (GBS) sera were severely reduced or eliminated as measured by radiolabel release. On introducing a source of fresh complement, the cr-EAE and GBS serum effects were largely restored whereas MS serum effects remained suppressed. Inactivation of serum complement with mercaptoethanol and Zymosan was associated with marked reduction in serum myelinotoxicity; some restoration of in vitro effects was possible on adding fresh complement although this occurred to a greater extent with cr-EAE and GBS than with MS sera. Inactivation of the alternative complement pathway brought a limited reduction in MS serum activity in vitro which was not restored with fresh complement. It is concluded that complement is involved only to a limited extent in MS serum myelinotoxic effects and that MS serum effects in vitro are due to several components of which thermolabile substances make a significant contribution and are as yet uncharacterised.