New paradigms in inflammation: where to next?

Abstract

In this issue of Immunological Reviews, articles are presented that cover many aspects of the newer biology of cytokines. It has been almost 50 years since the description of the interferons (IFNs) first hinted at the complex biology that formed the basis for immunity to infection. Since then, the field has moved through the description and characterization of macrophageactivating and inhibitory factors and various soluble mediators that influenced Tand B-cell behaviors. Even at these early points, the potential of the use of cytokines or cytokine antagonists as treatments to augment immunity, prevent immune hyperactivity, or influence the type of response was apparent and formed the basis for several of the early biotech companies. The pace accelerated through the 1980s with the application of molecular approaches to understand the basis for these activities, and the cloning of genes for numerous cytokines, costimulatory molecules, and death receptors started to reveal the molecular interactions that underpinned immunity. For example, the ability to study cytokine production provided the basis for the description of T-helper 1 (Th1) and Th2 subsets (1), and a framework emerged that allowed immunologists to probe models of how the immune system functioned during inflammation and how inappropriate immune responses could lead to disease. With the start of various genome projects in the 1990s, discovery-based programs intensified to a point where the list of interleukins (ILs), chemokines, tumor necrosis factor (TNF), and IFN family members was almost matched by the numbers of pattern recognition receptors that provided the foundation for the development of innate and adaptive responses. At this point, it seemed that with all this information and several dominant paradigms in place to explain how the immune system worked during inflammation, it was only a matter of time before this was translated into the development of new therapies to manage a spectrum of immune-mediated diseases. However, the challenge that then emerged was not Christopher A. Hunter Robert Kastelein

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