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Cytokines are soluble polypeptide mediators that control the growth, differentiation, and function of most cell types and play a particular role as mediators of inflammation. Cytokines form a network of interactive signals, some of which are stimulatory and others inhibitory. The physiologic roles of cytokines concern the coordination of processes between different cell types and the response to environmental stresses (Dinarello, 1996). With respect to the central nervous system (CNS), cytokines play a specific role and are particularly important in embryonic development, fever, neuroendocrine activation, and changes in behavior and mood. Furthermore, cytokines have been shown to be involved in numerous CNS disorders, such as cerebral ischemia, head trauma, apoptosis, regulation of the immune response to foreign antigens (HIV), and the development of cellular and humoral immunity and inflammatory responses (multiple sclerosis) (Rothwell and Hopkins, 1995). Thus, in the CNS, cytokines play a role in normal physiologic control, as well as being implicated in the pathogenesis of a number of neurologic diseases.

Interleukin-1 (IL-1), a 17-kDa glycoprotein, is one of several important cytokines involved in acute inflammatory responses (1). While IL-1 is produced primarily by monocytes and macrophages, it is also synthesized by astrocytes and microglial cells (1, 2). The IL-1 gene family is comprised of IL-lα,IL-1β, and the IL-1 receptor antagonist (IL-ira) (1, 3). IL-lα and IL-1β represent two unique proteins that are derived from two distinct human genes (1). IL-lβ is the predominant free extracellular form, whereas most IL-lα is membrane-bound. IL-lα and IL-1β are synthesized as precursor molecules, each with an approximate mol wt of 31 kDa. Processing of IL-lα and IL-1β to mature forms of 17 kDa requires specific cellular proteases (i.e., IL-lβ-converting enzyme, [ICE]). The mature forms of IL-lα and IL-lβ share 26% homology at the amino acid level and bind to the same IL-1 receptors (1, 3).