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with growth hormone, prolactin receptor (PRLR), and tumor necrosis factor with a ligand. In the case of
the human growth hormone-receptor complex and tumor necrosis factor-receptor complex the
interaction between the ligand and the receptor is intricate and takes place over a large area. It is likely
that this will be a characteristic feature of all cytokine-receptor complexes.
B. Cytokine-Based Therapy
Certain disease states can occur due to a disregulation of the cytokine network. This can lead to chronic
stimulation of the immune and inflammatory response and ultimately to disease. Many cytokines have
been implicated in autoimmune diseases like myasthenia gravis, insulin-dependent diabetes,
atherosclerosis, systemic lupus erythematosus, and rheumatoid arthritis [1,7,9]. The intimate relationship
between cytokines and the pathology of disease development and progress can be exploited to provide
therapeutic benefit. By subtly manipulating the cytokine communication network one can modulate the
disease process. Understanding of the functional roles of cytokines that mediate the communication
between them and the factors involved in the immune system's cell-cell interactions forms the
foundation for cytokine therapies. Such therapeutic agents are now a possibility due to modern
techniques such as molecular biology, structural biology, high-power computation, combinatorial
chemistry, and functional screening. The findings from biological techniques in conjunction with the
structural insights as obtained through protein crystallography and nuclear magnetic resonance form the
foundation for rational drug design [10–13]. Discovery of IL-1-based therapeutic agents have led to
promising applications in the treatment of the above mentioned diseases. Design of synthetic adjuvants,
for exogenous immunomodulation, is also an important factor to be considered in the field of vaccine
development. In this review we will discuss the available literature on interleukin-1 and the recent
attempts toward the design of immunomodulators.
II. The Interleukin-1 Family
The three molecules of the IL-1 family, interleukin-1α (IL-1α), interleukin-1β (IL-1β), and interleukin-1
receptor antagonist (IL-1Ra) map to the long arm of chromosome two in the human genome. It appears
that the family arose via a gene duplication event some 350 million years ago, and the molecules possess
between 27.5 and 36% sequence identity with each other (Table 2) [1,14,15]. In addition, the genes for
the two IL-1 receptors IL-1R1 and IL-1RII [16,17], and an IL-1R accessory protein (IL-1RacP), which
binds to the IL-1, IL-1 receptor complex [18], have been identified. Together, these molecules via their
differential activity serve primarily to modulate the host defense mechanism.
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