Cytokines: Interleukins

Abstract

The harmonious regulation of vital physiological processes, for example, replenishment of mature blood cells from bone marrow stem cells, termed hematopoiesis, and the activation of defense mechanisms against pathological microbes and injury has been shown to depend on the production and action of a variety of secreted biologically active proteins, collectively known as cytokines. Central among cytokines is a class of mediators, largely involved in the regulation of immune, inflammatory, and hematopoietic functions, designated interleukins primarily on the basis that interleukins are produced mainly by leukocytes and act locally on other leukocytes in surrounding tissues. Each interleukin, of which there are now 29 designated ones, exercises a spectrum of biological activities via specific cell surface receptors. Overlaps of biological activities have been found to be common among different interleukins and to result in many cases from the sharing of receptor components. On binding their cognate interleukins, receptors activate intracellular signaling pathways leading to the transcription of nuclear genes and expression of proteins necessary to commit the cell to a number of contingent events and responses according to the particular interleukin bound and cell type. Interleukins, however, probably rarely act alone and in vivo form complex interactive networks both among themselves and with other cytokines. Such complicated intercellular communications systems have made it difficult to precisely define the biological roles of interleukins in health and disease. In certain diseases, for example, cancer, some exogenously administered interleukins induce beneficial responses, but it has rarely been possible to dissociate their desirable pharmacological activities from their undesirable pharmacological activities, which often give rise to severe side effects. In fact, many disease symptoms, for example, fever, hypotensive shock, have been demonstrated to be strongly associated with the presence of endogenously produced interleukins, and this is leading to clinical evaluation of several interleukin antagonists in both acute and chronic diseases.