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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 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.
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