Immune regulation

Introduction The immune system in general responds appropriately to the presence of foreign antigens. However, there are certain diseases that arise from either a defective or over-responsive immune system on the part of the host. Two major therapeutic approaches are possible: either immunosuppression or immunopotentiation of the immune system. The object of this chapter is to introduce the reader to the various approaches that have been used to either suppress or stimulate the immune response. Several groups of drugs suppress the immune system (see Table 3.1). Among the oldest of these drugs are the corticosteroids, which have long been known to alter immune responses. When corticosteroids are given, the result is a transient lympho-penia peaking at four hours and lasting up to twenty-four hours. Helper T cells are predominantly affected, and at higher doses of steroids inhibition of interleukin-2 (IL-2) production by helper T cells becomes increasing important. Another major effect in humans is on resting macrophages (activated macrophages are not sensitive). In humans, steroids are used for two main purposes. One is the prevention or reversal of graft rejection (see Chapter 18). The other is in the treatment of autoimmune and malignant diseases. Corticosteroids modulate inflammation by suppressing cytokine- and chemokine-encoding genes, which inhibits the activation and recruitment of inflammatory cells. The side effects of steroids are numerous and often depend on both the dose used and duration of treatment. These include an increased susceptibility to infection, osteoporosis, and growth disturbances in children, as well as gastric ulcers, hypertension, acne, and hirsutism.