Differential effects of fosfomycin and corticosteroid on the molar ratio of interleukin-1 receptor antagonist/interleukin-1β in the culture supernatants of mononuclear phagocytes from patients with sarcoidosis

Mikuniya, Takeshi; Nagai, Sonoko; Takeuchi, Minoru; Izumi, Tatsuro

doi:10.1007/s10156-004-0335-1

Cited by 1 publication

(2 citation statements)

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Section: Figmentioning

confidence: 97%

“…For example, administration of the antibiotic fosfomycin to sarcoidosis patients increased the IL-1ra/IL-1␤ ratio in culture supernatants of mononuclear cells from these patients (Mikuniya et al, 2004). In contrast, the corticosteroid prednisolone lowered the IL-1ra/IL-1␤ ratio (Mikuniya et al, 2004). Gamma-linolenic acid (GLA) is an anti-inflammatory lipid that can reduce joint inflammation, and it has been shown to increase the IL-1ra/IL-1␤ ratio in monocytes from rheumatoid arthritis patients (Furse et al, 2002).…”

Section: Figmentioning

confidence: 99%

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Inflammation in Human Brain Injury: Intracerebral Concentrations of IL-1α, IL-1β, and Their Endogenous Inhibitor IL-1ra

Hutchinson

O’Connell

Rothwell

et al. 2007

Journal of Neurotrauma

175

109

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Following traumatic brain injury (TBI), cascades of inflammatory processes occur. Laboratory studies implicate the cytokines interleukin-1alpha (IL-1alpha) and IL-1beta in the pathophysiology of TBI and cerebral ischemia, whilst exogenous and endogenous interleukin-1 receptor antagonist (IL-1ra) is neuroprotective. We analyzed IL-1alpha, IL-1beta, and IL-1ra in brain microdialysates (100-kDa membrane) in 15 TBI patients. We also analyzed energy-related molecules (glucose, lactate, pyruvate, glutamate, and the lactate/pyruvate ratio) in these brain microdialysates. Mean of mean (+/-SD) in vitro microdialysis percentage recoveries (extraction efficiencies) were IL-1alpha 19.7+/-7.6%, IL-1beta 23.9+/-10.5%, and IL-1ra 20.9+/-6.3%. In the patients' brain microdialysates, mean of mean cytokine concentrations (not corrected for percentage recovery) were IL-1alpha 5.6+/-14.8 pg/mL, IL-1beta 10.4+/-14.7 pg/mL, and IL-1ra 2796+/-2918 pg/mL. IL-1ra was consistently much higher than IL-1alpha and IL-1beta. There were no significant relationships between IL-1 family cytokines and energy-related molecules. There was a significant correlation between increasing IL-1beta and increasing IL-1ra (Spearman r=0.59, p=0.028). There was also a significant relationship between increasing IL-1ra and decreasing intracranial pressure (Spearman r=-0.57, p=0.041). High concentrations of IL-1ra, and also high IL-1ra/IL-1beta ratio, were associated with better outcome (Mann Whitney, p=0.018 and p=0.0201, respectively), within these 15 patients. It is unclear whether these IL-1ra concentrations are sufficient to antagonize the effects of IL-1beta in vivo. This study demonstrates feasibility of our microdialysis methodology in recovering IL-1 family cytokines for assessing their inter-relationships in the injured human brain, and suggests a neuroprotective role for IL-1ra. It remains to be seen whether exogenous IL-1ra or other agents can be used to manipulate cytokine levels in the brain, for potential therapeutic effect.

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Section: Figmentioning

confidence: 97%