Drugs which Affect the Production of Cytokines

See also factors affecting Th1/Th2 development        See also cytokines secreted during Th development

A number of proteins which act as antagonists (inhibit) the biological activity of cytokines also exist. These proteins can do this by either binding directly to a cytokine receptor (but failing to activate the cell) or by binding directly to the cytokine itself.

Glucocorticoids act on APCs to supress the production of the main inducer of Th1 responces which is IL-12. Since IL-12 is very potent in enhancing IFN-γ and inhibiting IL-4 synthesis by T cells, the inhibition of IL-12 production may represent a major mechanism by which glucocorticoids affect the Th1/Th2 balance. Indeed, clucocorticoid treated monocytes/macrophages produce significantly less Il-12, leading to a decreased capacity of these cells to induce INF-γ production by antigen primed CD4+ T cells. The same treatment is also associated with an increased proudction of IL-4 by T cells, probably resulting from disinhibition from the supressive effects of IL-12 on Th2 activity.

Catecholamines such as norepinephrine and epinephrine drive a Th2 shift both at the level of APCs and Th1 cells. Both potently inhibit or enhance the production of IL-12 and IL-10, respectively in human whole blood cultures stimulated with LPS.

Histamine is a well recognized mediator of acute inflammation and allergic reactions. These actions are mainly mediated by activation of H1 histamine receptors and include vasodilation, increased permeability of the vessel wall and edema. Histamine may also have important immunoregulatory functions via H2 receptors expressed on immune cells. For example, histamine inhibits TNFα but potentiates IL-6 production. Because TNFα is primarily a type 1 cytokine and IL-6 promotes B cell differentiation, this suggests that histamine may promote humoral immunity. Histamine also inhibits the secretion of human IL-12 and stimulates the production of IL-10 in whole blood and monocyte cultures stimulated with LPS.