{"title":"The Fun Continues","authors":"John Montgomery","doi":"10.4324/9781003267669-3","DOIUrl":"https://doi.org/10.4324/9781003267669-3","url":null,"abstract":"","PeriodicalId":214669,"journal":{"name":"Comedy Films 1894–1954","volume":"66 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128634516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Roaring Twenties","authors":"John Montgomery","doi":"10.4324/9781003267669-9","DOIUrl":"https://doi.org/10.4324/9781003267669-9","url":null,"abstract":"Cytokines have come a long way since the initial description of macrophage inhibitory factor in the 1960s (David, 1966; Bloom and Bennett, 1966). For years, immunologists marveled over the potency of these molecules to push, pull, and otherwise cajole a myriad of cells to do just about anything in various 96-well experimental settings. The therapeutic advances of anti-tumor necrosis factor (TNF) therapies in chronic inflammatory bowel and joint diseases and of interferona (IFN-a) in multiple sclerosis and hepatitis C virus infection moved the field beyond the broadband approaches epitomized by the use of steroids and broad-acting immunosuppressives, however, and demonstrated that more precise targeting of the immune system was possible. Here, understanding the language of the cytokines will be imperative. Various colony-stimulating factors have been exploited for bone marrow reconstitution (not without their own toxicities), but otherwise the staggering multiplicity of actions has cut short the broad use of these agents in human disease. Most of the cytokines exist within multiple family members and share combinatorial subunits and/or receptor-recognition modules, suggesting that evolution likes these things but also that nuanced differences probably exist among closely related family members and that these must be recognized before the potential therapeutic uses of these cytokines can be optimized. As updated by Scheinecker et al. among the series of reviews that follow, therapeutic targeting of interleukin-1 (IL-1), IL-6, and additional biomodulators extends the pharmacopoeia of immune intervention in inflammatory diseases, but precisely how to organize the rational approach for the use of anticytokine therapies remains too often empiric (Scheinecker et al. [2008], this issue of Immunity). The series of review articles in this issue address recent subjects of much currency in the cytokine field. Of note, the discovery of additional CD4 T cell subsets that round out the canonical T helper 1 (Th1) and Th2 cell subsets first described in the 1980s emerges as a constant theme (Figure 1). Because of their capacity to become long-lived memory effector cells, these various populations of helper T cells can underpin many chronic inflammatory states mediated by cytokines when left unregulated. The Th1 and Th2 paradigm drove substantial discoveries in the immune system, perhaps most importantly the linking of epigenetic alterations at sites of expressed cytokines with canonical ‘‘master transcriptional regulators’’ whose binding could drive cell-fate decisions, thus providing a mechanism by which gene expression and cellular functions become stabilized (reviewed in Ansel et al., 2006; Lee et al., 2006). These findings in turn were driven by a quiet revolution in immunology. Over the past 20 years, 96-well-plate experiments were replaced by challenges using pathogens of every sort to tweak living animals in order to probe the functions of cells and, indir","PeriodicalId":214669,"journal":{"name":"Comedy Films 1894–1954","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124761745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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