Cytokines as Mediators of Autoimmune Diabetes and Diabetic Complications

CYTOKINES are molecularly distinct secretory proteins recognized by their common function as intercellular signals. In contrast to hormones, cytokines influence cellular activities largely within confined environs in an autocrine or paracrine fashion and infrequently achieve detectable levels in the circulation. Many cytokines were initially described as cellular “factors” or “activities” contained within experimental tissue culture supernatants. The advent of molecular biology has allowed for the identification, isolation, and characterization of individual cytokine genes and consequently the expression of virtually unlimited quantities of purified protein. Members of the cytokine family include interleukins (IL) (lymphokines and monokines), interferons (IFN), colony-stimulating factors, and peptide growth factors (1). In general, cytokines are glycoproteins of 100–200 amino acid residues. Most cytokines are translated along with an aminoterminal signal peptide that directs the polypeptide chain to the endoplasmic reticulum for processing and secretion. Exceptions to this process are the cytokines IL-lα and IL-1β (2). These proteins lack signal sequences, yet are secreted. In addition, they can bind to the plasma membranes of their cells of origin in a bioactive precursor form (2). The regulatory signals controlling cytokine transcription, translation, and secretion also differ among the various cytokines. For example, the IL are tightly regulated by specific activation events that occur within a limited number of cell types (3). In contrast, the interferons and growth factors are ubiquitously produced by many cell types in response to a variety of stimuli including injury, viral infection, and metabolic disturbances.