Medical brain notes 37

  Interferons and Interleukins INTRODUCTION In 1957 a substance was described (Isaacs and Lindenmann, 1957) that was produced by virus-infected cell cultures and “interfered” with infection by other viruses; it was called interferon (IFN). Over the following decades it was realized that “IFN” comprises a family of related proteins with several additional properties. Starting in the 1960s various “factors” produced primarily by white blood cells (WBC) as well as other cell supernatants were described which acted in various ways on other WBCs or somatic cells. They were usually given a descriptive name either associated with their cell of origin or their activity on other cells resulting in a myriad of names. The application of molecular technology allowed us to determine that some cyto-kines had multiple activities and that different cyto-kines had similar overlapping activities. A systematicclassification based on genetic structure and protein characterization has been effective. T...

  INTERFERONS: NOMENCLATURE AND FUNCTIONS   IFNs are a family of naturally occurring proteins and glycoproteins with molecular weights of 16,776 to 22,093 Da produced and secreted by cells in response to viral infections and to synthetic or biological inducers. By interacting with their specific hetero-dimeric receptors on the surface of cells, the IFNs initiate a broad and varied array of signals that induce cellular antiviral states, modulate inflammatory re-sponses, inhibit or stimulate cell growth, produce or inhibit apoptosis, and modulate many components of the immune system. Structurally, they are part of the helical cytokine family (Fig. 1). During the past 25 years, major research efforts have been undertaken to understand the signaling mechanisms through which these cytokines induce their effects. Figure 2, as an example, illustrates the Janus-activated kinase–signal transducer and activator of transcrip-tion (JAK-STAT), the best characterized IFN signaling pathway. ...

  INTERLEUKINS: NOMENCLATURE AND FUNCTIONS ILs are primarily a collection of immune cell growth, differentiation and maturation factors. Collectively they orchestrate a precise and efficient immune response to toxins and pathogens, including cancer cells, recognized as foreign. As is the case for IFNs, ILs bind to related specific cell surface receptors which activate similar intracellular signaling cascades (Lutfalla et al., 2003; Pestka et al., 2004b; Huising et al., 2006). Many ILs, primarily those with proin-flammatory function, are intrinsically toxic either directly or indirectly, i.e., through induction of toxic gene products. Therefore the human body has an elaborate system of checks and balances that, under (patho)-physiological conditions, regulates the mag-nitude and duration of an immune response. Under biological conditions, ILs usually have a short circulation time, and their production is regulated by positive and negative feedback loops. Furthermore their effect is ...