Environmentally induced autoimmune diseases: Potential mechanisms

Environmental and other xenobiotic agents can cause autoimmunity. Examples include drug-induced lupus, toxic oil syndrome, and contaminated L-tryptoph an ingestion. Numerous mechanisms, based on in vitro evidence and animal mo dels, have been proposed to explain how xenobiotics induce or accelerate au toimmunity. The majority of these can be divided into three general categor ies. The first is those inhibiting the processes involved in establishing t olerance by deletion. Inhibiting deletion can result in the release of newl y generated autoreactive cells into the periphery. The second mechanism is the modification of gene expression in the cells participating in the immun e response, permitting lymphocytes to respond to signals normally insuffici ent to initiate a response or allowing the antigen-presenting cells to abno rmally stimulate a response. Abnormal gene expression can thus disrupt tole rance maintained by suppression or anergy, permitting activation of autorea ctive cells. The third is the modification of self-molecules such that they are recognized by the immune system as foreign. Examples illustrating thes e concepts are presented, and related mechanisms that have the potential to similarly affect the immune system are noted. Some mechanisms appear to be common to a variety of agents, and different mechanisms appear to produce similar diseases. However, evidence that any of these mechanisms are actual ly responsible for xenobiotic-induced human autoimmune disease is still lar gely lacking, and the potential for numerous and as yet unidentified mechan isms also exists.