HEAT-SHOCK PROTEINS AS POTENTIAL TARGETS IN THE THERAPY OF INFLAMMATORY ARTHRITIS

Whether heat shock proteins (hsp) will be therapeutic targets in arthr itis depends on their role in pathogenesis. In this article, three pos sibilities are considered. Firstly, an excessive immune response to ba cterial hsp could be arthritogenic - as may occur in reactive arthriti s. In these circumstances therapy would be directed to downregulating this immune response, or altering the nature of the immune response e. g. by changing cytokine production from interferon-g to IL-4. However this approach depends on the immune response to bacterial hsp not bein g critical for control of the bacterial infection. Secondly, an immune response to bacterial hsp may induce autoimmunity by cross-reactivity , e.g. with the homologous human. This could also be modulated in the same way with a lower likelihood of interfering with control of the in fectious agent, since only a component of the immune response against the bacterial hsp will be cross-reactive with self. Thirdly, recent ex periments raise the possibility that joint inflammation might be contr olled by T cells which recognizes self hsp, particularly hsp60. Therap ies might enhance this response; protection from experimental arthriti s by prior immunization with hsp60 is well established. Whether simila r approaches will be viable after arthritis is established remains to be seen.