TOXIC QUINONES PRODUCED BY MAMMALIAN DEFENSE CELLS - CAUSATIVE AGENTSFOR AUTOIMMUNE REACTIONS

Multiple sclerosis is a disease both of the CNS compartment in which a localized immune response occurs, and of the peripheral immune compar tment. The causative agent is unknown, though viruses are suspected to be among the candidates. Here a hypothesis is proposed, that apart fr om viruses, also activated granulocytes of the host might trigger a se nsitization against self, insofar as they are suited to modify self-pr oteins. The modification results from the action of endogenous o-quino nes which are generated by activated granulocytes. o-quinones are chem ically reactive and couple to proteins producing new epitopes. Modifie d self-proteins then may sensitize the immune system or break the immu ne tolerance. Granulocytes thus not only effectively eliminate pathoge ns, but cause damage to tissues of the host, by proteinases as describ ed in inflammation, or by endogenous o-quinones as proposed here for m ultiple sclerosis and its models.