title: Cytokines: The Good, the Bad, and the Deadly.
abstract: Over the past 30 years, the world of pharmaceutical toxicology has seen an explosion in the area of cytokines. An overview of the many aspects of cytokine safety evaluation currently in progress and evolving strategies for evaluating these important entities was presented at this symposium. Cytokines play a broad role to help the immune system respond to diseases, and drugs which modulate their effect have led to some amazing therapies. Cytokines may be "good" when stimulating the immune system to fight a foreign pathogen or attack tumors. Other "good" cytokine effects include reduction of an immune response, for example interferon β reduction of neuron inflammation in patients with multiple sclerosis. They may be "bad" when their expression causes inflammatory diseases, such as the role of tumor necrosis factor α in rheumatoid arthritis or asthma and Crohn's disease. Therapeutic modulation of cytokine expression can help the "good" cytokines to generate or quench the immune system and block the "bad" cytokines to prevent damaging inflammatory events. However, care must be exercised, as some antibody therapeutics can cause "ugly" cytokine release which can be deadly. Well-designed toxicology studies should incorporate careful assessment of cytokine modulation that will allow effective therapies to treat unmet needs. This symposium discussed lessons learned in cytokine toxicology using case studies and suggested future directions.
authors.affiliation: Huntingdon Life Sciences, Somerset, NJ, USA ramanit@princeton.huntingdon.com.
authors.forename: Thulasi
authors.initials: T
authors.lastname: Ramani
authors.affiliation: Huntingdon Life Sciences, Somerset, NJ, USA.
authors.forename: Carol S
authors.initials: CS
authors.lastname: Auletta
authors.affiliation: Janssen R&D, LLC, Spring House, PA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weinstock
authors.affiliation: ToxStrategies, Inc, Bend, Oregon, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mounho-Zamora
authors.affiliation: MedImmune, Gaithesburg, MD, USA.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Ryan
authors.affiliation: Bristol Myers Squibb Company, New Brunswick, NJ, USA.
authors.forename: Theodora W
authors.initials: TW
authors.lastname: Salcedo
authors.affiliation: Huntingdon Life Sciences, Somerset, NJ, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Bannish
mesh_terms: D000818:Animals; D003226:Congresses as Topic; D016207:Cytokines / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D018675:Toxicity Tests
chemical_list: D016207:Cytokines
keywords: biomarkers; biotherapeutics; cytokine release syndrome; cytokines; immunomodulators