title: Evidence for activin A and follistatin involvement in the systemic inflammatory response.
abstract: The inflammatory cascade is a multifactorial process regulated by interwoven cytokine and growth factor networks. This review summarizes the emerging evidence that implicate activin A and follistatin in inflammatory processes. Our recent studies have determined that activin A is released early in the cascade of circulatory cytokines during systemic inflammatory episodes, roughly coincident with tumour necrosis factor (TNF)-alpha and before interleukin (IL)-6 and follistatin. The source(s) of this activin A are not yet established, but prime candidates are monocytes/macrophages, other immune cell types or vascular endothelial cells. Clinical data are limited, but activin beta(A) subunit mRNA or activin A protein is elevated in inflammatory bowel diseases and inflammatory arthropathies, and circulating concentrations of follistatin are elevated in patients with sepsis. In more mechanistic approaches, in vitro studies show that activin A can have both pro- and anti-inflammatory actions on key inflammatory mediators such as TNFalpha, IL-1beta and IL-6. Furthermore, there is emerging understanding of how the intracellular signaling pathway for activin A, incorporating Smads, may interact with and be modulated by other key regulatory cytokines and growth factors.
authors.affiliation: Monash Institute of Reproduction and Development, Monash University, Vic. 3168, Melbourne, Australia. david.phillips@med.monash.edu.au
authors.forename: D J
authors.initials: DJ
authors.lastname: Phillips
authors.forename: K L
authors.initials: KL
authors.lastname: Jones
authors.forename: J Y
authors.initials: JY
authors.lastname: Scheerlinck
authors.forename: M P
authors.initials: MP
authors.lastname: Hedger
authors.forename: D M
authors.initials: DM
authors.lastname: de Kretser
mesh_terms: D028341:Activins / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D004347:Drug Interactions; D038681:Follistatin; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D028322:Inhibin-beta Subunits / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D038681:Follistatin; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits