Glucocorticoids and Th-1, Th-2 type cytokines in rheumatoid arthritis, osteoarthritis, asthma, atopic dermatitis and AIDS.

Endogenous or exogenous glucocorticoids play a key role in the control of the immune and inflammatory network. Regulation of the effects of the glucocorticoids depends on changes in therapeutic levels, but also, as recently discovered, on modifications of the binding characteristics of the glucocorticoid receptors of target cells. In rheumatoid arthritis (RA), chronic bronchial asthma, atopic dermatitis, in chondrocytes from osteoarthritic patients, and in advanced stages of HIV infection, there is a down-regulation of the glucocorticoid receptors. As a consequence, B cell immune proliferation is stimulated in RA, proteolysis is enhanced in osteoarthritis, the glucocorticoids' therapeutic effect is reduced in asthma and atopic dermatitis, and a chronic persistent increase of interferon alpha is seen in HIV. Finally, glucocorticoids are also capable of switching CD4 cells from a Th-1 to a Th-2 pattern. A decreased affinity of lymphocyte glucocorticoid receptors could hinder such a switch, with obvious clinical implications.