Cytokines and their antagonists as therapeutic agents

Cytokines are powerful molecules that the body's immune cells secrete in response to an offending agent. Their main function is to direct the immune response into the most effective pathway that will eventually result in elimination of the offender. The last decade was marked by an enormous and ever growing interest that led to discovery of numerous cytokine molecules and their amazing influence on the body immune function. The more we are learning about the way cytokines modulate and direct the immune responses of the body, the interest in using them or their antagonist to change or enhance those responses is growing. Studies are currently underway showing the beneficial effect of TNFalpha antagonists on the cellular injury mediated by this cytokine in rheumatic diseases, inflammatory bowel disease and endotoxemia. Interferon therapies are also tested utilizing IFNalpha for treatment of Hepatitis B and C. The discovery of Th1 and Th2 cytokines had shown that the nature of the immune response is, in essence, directed by a few important cytokines. Which immune reactions will develop seems to depend on whether IL-2 and IL-12 are secreted (and the immune response becomes Th1 with secretion of IFNgamma and efficient removal of some antigens such as viruses) or IL-4 is secreted in which case Th2 response results in down regulation of IFNgamma and IL-2 secreting effectors. The discovery, isolation and purification of these molecules open the possibility to skew the immune response in order to facilitate better outcome. For example, studies have now being conducted aimed at using IL-2 as an adjuvant therapy in conjunction with HAART in HIV patients. Similarly, IL-12 seems to be beneficial in melanoma and has been used as a very potent adjuvant for eliciting immune responses to immunization. Furthermore, studies with IL-4 knockout mice and those utilizing IL-4 blocking agents have shown that this cytokine might play a crucial role in maintaining persistent viral infections and in mediating chronic, autoimmune diseases. Using body's own immunomodulators is becoming an exciting possibility to target inefficient or misdirected immune responses that result in disease. The potential benefits in terms of human disease are enormous and still largely unexplained. Thus, using cytokines and their antagonists as therapeutic agents is an emerging and growing area of research.