Clinical Information

Cytokines are important mediators of cell-to-cell communication within the innate and adaptive immune systems. The expression of most cytokines is highly regulated and generally occurs in response to foreign or self-antigenic stimulation. The functions of cytokines are extremely varied, with many cytokines also displaying pleiotropic effects, depending on their cellular target. Some cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-1 beta, IL-6, interferon (IFN)-alpha and beta, IL-10, and IL-18 are particularly important in the innate immune response. For example, TNF, IL-1 beta, and IL-6 induce expression of acute phase proteins in the liver. TNF and IL-1 beta also lead to endothelial activation and are critical regulators of the hypothalamus, which can result in elevated body temperature. IL-6, in comparison, is a bridge to the adaptive immune response, by acting on B cells to induce proliferation. In contrast, IFN-alpha and IFN-beta (members of the type I IFN family) are key components of the innate immune response to viral infections. IFN-gamma, which is a type II IFN, has roles in both the innate and adaptive immune responses, including macrophage activation, induction of B-cell isotype switching, and T helper type 1 (Th1) cell differentiation. Other cytokines, such as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha), are categorized as chemokines because they function primarily to attract leukocytes to the site of inflammation. Further, some cytokines act on hematopoietic stem cells to induce differentiation of various leukocytes. For example, granulocyte-monocyte colony stimulating factor (GM-CSF) induces myeloid progenitor cells to differentiate into neutrophils and monocytes. Lastly, for some cytokines, soluble forms of the receptor can be found in the peripheral circulation. The IL-2 soluble receptor is produced from proteolytic cleavage of the membrane-bound receptor, which occurs during T-cell activation. As a group, cytokines and their receptors represent a highly complex and critical regulator of a normal immune response.