title: The role of interleukin-1 and interleukin-18 in pro-inflammatory and anti-viral responses to rhinovirus in primary bronchial epithelial cells.
abstract: Human Rhinovirus (HRV) is associated with acute exacerbations of chronic respiratory disease. In healthy individuals, innate viral recognition pathways trigger release of molecules with direct anti-viral activities and pro-inflammatory mediators which recruit immune cells to support viral clearance. Interleukin-1alpha (IL-1α), interleukin-1beta (IL-1β) and interleukin-18 (IL-18) have critical roles in the establishment of neutrophilic inflammation, which is commonly seen in airways viral infection and thought to be detrimental in respiratory disease. We therefore investigated the roles of these molecules in HRV infection of primary human epithelial cells. We found that all three cytokines were released from infected epithelia. Release of these cytokines was not dependent on cell death, and only IL-1β and IL-18 release was dependent on caspase-1 catalytic activity. Blockade of IL-1 but not IL-18 signaling inhibited up-regulation of pro-inflammatory mediators and neutrophil chemoattractants but had no effect on virus induced production of interferons and interferon-inducible genes, measured at both mRNA and protein level. Similar level of virus mRNA was detected with and without IL-1RI blockade. Hence IL-1 signaling, potentially involving both IL-1β and IL-1α, downstream of viral recognition plays a key role in induction of pro-inflammatory signals and potentially in recruitment and activation of immune cells in response to viral infection instigated by the epithelial cells, whilst not participating in direct anti-viral responses.
authors.affiliation: Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Cambridge, United Kingdom.
authors.forename: Siân C
authors.initials: SC
authors.lastname: Piper
authors.forename: John
authors.initials: J
authors.lastname: Ferguson
authors.forename: Linda
authors.initials: L
authors.lastname: Kay
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Parker
authors.forename: Ian
authors.initials: I
authors.lastname: Sabroe
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Sleeman
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Briend
authors.forename: Donna K
authors.initials: DK
authors.lastname: Finch
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D019898:Autocrine Communication; D001980:Bronchi / Q000473:pathology*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006367:HeLa Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D010850:Picornaviridae Infections / Q000378:metabolism / Q000821:virology; D012229:Rhinovirus / Q000502:physiology*; D015398:Signal Transduction; D019562:Viral Load; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D018836:Inflammation Mediators; D007375:Interleukin-1; D020382:Interleukin-18; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D020170:Caspase 1