S. Lightman - Böcker

The eye can become involved in immune-mediated diseases that affect it alone or as part of a multi-organ disease process. Much immunological attention has been focused on other organs affected by these processes and the subject of the immunology of eye diseases is a relatively new one. Many of these diseases that involve the eye are not life-threatening but can result in devastat­ ing loss of sight that if bilateral, will have major effects on the patient's life. Systemic immunological investigations are generally unhelpful in these patients and one of the major problems in this field has been the lack of diseased tissue available for examination to determine the pathological processes involved. Our poor understanding of basic mechanisms of disease in the eye has meant that treatment of many of these conditions is often inadequate. It has become possible to apply in the eye many ofthe techniques used to investigate the role of the immune system in other systems. Animal models of many of the disease processes have also allowed dissection of the immune response both within and outside the eye. It is my belief that a greater understanding of the mechanisms by which the structures in the eye become damaged will allow more specific and effective therapeutic strategies to be devised.

The fact that certain adrenal steroid hormones are immunosuppressive and anti-inflammatory has been known for many years, and is routinely exploited by physicians. These effects are attributable to glucocorticoid steroids such as cortisol. Pharmacological doses of glucocorticoids inhibit most or all T cell types. However we now know that the effect of exposure to raised physiological levels is mainly to drive developing lymphocyte responses towards a Th2 cytokine profile (interleukin-4 secreting) while suppressing the development ofThi (gamma interferon- secreting) lymphocytes. Only recently have two further regulatory mechanisms become appar- ent. First, these effects of cortisol are balanced by pro-inflammatory and ThI-enhancing effects of another adrenal steroid, dehydroepiandro- sterone sulfate (DHEAS). Second, the activity of cortisol is directly modulated by enzymes in the target organs and lymphoid tissues that convert it into inactive cortisone. This new information leads to the possibility that immunoregulatory steroids could be used by physicians in novel ways.We can envisage steroid combinations that exploit the anti-inflammatory effects of corti- sol, while the Thi-suppressing and Th2-promoting properties of these hormones are opposed by derivatives of DHEAS. Such therapies are already proving effective in animal models of infection, and could revol- utionize treatment of Th2-mediated diseases such as asthma, where the anti-inflammatory effects of cortisol are desirable but the effects on T lymphocyte differentiation are not.