IL-12 as a therapeutic target for pharmacological modulation in immune-mediated and inflammatory diseases:: regulation of T helper 1/T helper 2 responses

1 Interleukin-12 (IL-12) is a pivotal cytokine in driving the immune system towards a T helper (Th) 1 type response and preventing a Th2 type immune profile. Therefore, IL-12 is indispensable in the defense against certain, mainly intracellular pathogens, but overproduction of this cytokine is crucially involved in the etiology of several inflammatory and autoimmune diseases. 2 Hence, IL-12 is an ideal target for pharmacological intervention in the therapy of autoimmune and inflammatory diseases. 3 The production of IL-12 and a resultant Th1 type immune response can be suppressed with several pharmacological approaches including modulation of intracellular cyclic AMP levels, glucocorticoids and nuclear factor-kappa B inhibition. IL-12 responsiveness may be inhibited using anti-IL-12 antibodies, soluble IL-12 receptors or the IL-12 p40 homodimer. 4 Exploitation of these approaches may provide novel means for the experimental therapy of a variety of pathophysiological states.