PT  - JOURNAL ARTICLE
AU  - Laura McCulloch
AU  - Stuart M. Allan
AU  - Craig J. Smith
AU  - Barry W. McColl
TI  - Interleukin-1 receptor antagonist treatment in acute ischaemic stroke does not alter systemic markers of anti-microbial defence
AID  - 10.1101/587881
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 587881
4099  - http://biorxiv.org/content/early/2019/03/26/587881.short
4100  - http://biorxiv.org/content/early/2019/03/26/587881.full
AB  - Aim 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 stroke-associated 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 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-1Ra-treated 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 anti-microbial mediators.CRPC-Reactive proteinIL-1RaIL-1 receptor antagonistMBLmannose-binding lectinNIHSSNational Institute of Health Stroke ScaleSNSsympathetic nervous systemWBCWhite blood cell