Interleukin-1 receptor antagonist treatment in acute ischaemic stroke does not alter systemic markers of anti-microbial defence

Laura Mcculloch, Stuart M. Allan, Hedley C. Emsley, Craig J. Smith, Barry W. Mccoll

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Blockade of the cytokine interleukin-1 (IL-1) with IL-1 receptor antagonist (IL- 1Ra) is a candidate treatment for stroke entering phase II/III trials, which acts by inhibiting harmful inflammatory responses. Infection is a common complication after stroke that significantly worsens outcome and is related to stroke-induced deficits in systemic immune function thought to be mediated by the sympathetic nervous system. Therefore, immunomodulatory treatments for stroke, such as IL-1Ra, carry a risk of aggravating strokeassociated infection. Our primary objective was to determine if factors associated with antibody-mediated antibacterial defences were further compromised in patients treated with IL-1Ra after stroke.
Methods: We assessed plasma concentrations of immunoglobulin isotypes and complement components in stroke patients treated with IL-1Ra or placebo and untreated non-stroke controls using multiplex protein assays. Activation of the sympathetic nervous system (SNS) was determined by measuring noradrenaline, a major SNS mediator.
Results: There were significantly lower plasma concentrations of IgM, IgA, IgG1 and IgG4 in stroke-patients compared to non-stroke controls, however there were no differences between stroke patients treated with placebo or IL-1Ra. Concentrations of complement components associated with the classical pathway were increased and those associated with the alternative pathways decreased in stroke patients, neither being affected by treatment with IL- 1Ra. Noradrenaline concentrations were increased after stroke in both placebo and IL-1Ratreated stroke patients compared to non-stroke controls.
Conclusion: These data show treatment with IL-1Ra after stroke does not alter circulating immunoglobulin and complement concentrations and is therefore unlikely to further aggravate stroke-associated infection susceptibility through reduced availability of these key antimicrobial mediators.
Original languageEnglish
Pages (from-to)1039
JournalF1000Research
Volume8
Early online date10 Jul 2019
DOIs
Publication statusPublished - 2019

Keywords

  • stroke
  • IL-1Ra
  • immunoglobulins
  • complement
  • infection

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