Stress proteins as targets for anti-inflammatory therapies.
Microbial heat shock proteins (HSPs) are ubiquitous and highly immunogenic. In healthy humans, B- and T-cells with specificity for self-HSP can be easily detected. In patients with chronic inflammatory diseases, raised levels of antibodies and T-cells with reactivity to self-HSP have been observed. Based on this and other evidence, this raised immune reactivity might be the result of stress-induced upregulation of self-HSP during inflammation and is possibly caused by tissue destruction. More importantly, immunization with conserved sequences of microbial-HSP increases resistance to the induction of autoimmune disease. Together, it appears that immune reactivity directed towards self-HSP can be part of a regulatory immune effector mechanism that contributes to maintenance of self-tolerance and has anti-inflammatory activity. Boosting of such anti-inflammatory effector mechanisms by artificial immunization offers attractive immunotherapeutic possibilities.
van Eden I
Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, University of Utrecht Yalelaan 1, 3584CL Utrecht, The Netherlands.