Clinical and experimental immunology
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Clin. Exp. Immunol. · Dec 2013
Randomized Controlled TrialImmune-monitoring in Kawasaki disease patients treated with infliximab and intravenous immunoglobulin.
The expansion of regulatory T cells (Treg ) controls inflammation in children with acute Kawasaki disease (KD). Blockade of tumour necrosis factor (TNF)-α is an emerging therapy for KD patients with refractory inflammation, but there is concern that this therapy could impede the host immune regulation. To define the effect of TNF-α blockade, we conducted ex-vivo immune-monitoring in KD subjects who participated in a randomized, double-blind, placebo-controlled clinical trial of the addition of infliximab to standard intravenous immunoglobulin (IVIG) therapy. ⋯ We also defined tolerogenic mDC that expand in the subacute phase of KD not impaired by infliximab treatment. Treg and Tmem expanded after treatment with no significant differences between the two groups. Treatment of KD patients with infliximab does not adversely affect generation of tolerogenic mDC or the development of T cell regulation and memory.
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Clin. Exp. Immunol. · Oct 2012
Randomized Controlled TrialDifferential effects of infliximab on absolute circulating blood leucocyte counts of innate immune cells in early and late rheumatoid arthritis patients.
Anti-tumour necrosis factor (TNF) biologics have revolutionized therapy of rheumatoid arthritis (RA). We compared the effects of infliximab on numbers of circulating leucocyte subsets in early RA (disease/symptom duration of ≤1 year) and late RA patients (>1 year). A control group consisted of early RA patients treated with a combination of methotrexate (MTX) and methylprednisolone. ⋯ CD16(+) granulocytes, NK cells and CD14(dim) monocytes all expressed higher levels of mTNF in RA patients. In summary infliximab is associated with decreased CD16(+) granulocyte and NK cell counts, possibly through binding of mTNF. Differential effects of infliximab between early and late RA suggest that pathogenic mechanisms change as disease progresses.
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Clin. Exp. Immunol. · Jul 2010
Randomized Controlled Trial Comparative StudyOral non-typable Haemophilus influenzae enhances physiological mechanism of airways protection.
Oral immunotherapy with inactivated non-typeable Haemophilus influenzae (NTHi) prevents exacerbations of chronic obstructive pulmonary disease, but the mechanism is unclear. The aim of this study was to determine the mechanism of protection. This was a placebo versus active prospective study over 3 months in 64 smokers. ⋯ These data are consistent with T cell priming of gut lymphoid tissue by aspiration of bronchus content into the gut, with oral immunotherapy augmenting this process leading to enhanced bronchus protection. The evidence for protection was a stable IgG antibody level through the study in the oral NTHi treatment group, contrasting with an increase in antibody correlating with exposure of the airways to H. influenzae in the placebo group. Saliva lysozyme was a useful biomarker of mucosal inflammation, falling after oral NTHi consistent with a reduction in the level of intralumenal inflammation.
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Clin. Exp. Immunol. · Apr 2006
Randomized Controlled TrialShort-term simvastatin treatment has no effect on plasma cytokine response in a human in vivo model of low-grade inflammation.
Statins reduce plasma cholesterol, but clinical trials and in vitro studies indicate that they might also possess anti-inflammatory properties. The effect of simvastatin on circulating cytokines and leucocytes was evaluated in a human in vivo model of low-grade inflammation. Thirty young healthy male participants received an injection of the bacterial cell wall product endotoxin (0.06 ng/kg) to induce systemic inflammation. ⋯ Plasma cytokines as well as total leucocyte counts increased in all participants upon endotoxin challenge but were not affected by simvastatin treatment. Tolerance to endotoxin was observed in both groups after 14 days. Short-term treatment with simvastatin (20 mg/day) did not influence circulating cytokine levels during endotoxaemia in this human in vivo study.
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Clin. Exp. Immunol. · Aug 1995
Randomized Controlled Trial Comparative Study Clinical TrialComparison of two types of intravenous immunoglobulins in the treatment of neonatal sepsis.
In a prospective double-blind study, standard intravenous immunoglobulin (IVIG) was compared with an IgM-enriched IVIG in the treatment of neonatal sepsis. The two treatment groups were also compared with matched controls. One hundred and thirty babies (65 in each group) ranging from 0 to 24 days old, 480 to 4200 g in weight and born between 24 and 42 weeks of gestation who had, or were suspected of having, sepsis were given either standard IVIG or IgM-enriched IVIG (250 mg/kg per day) for 4 days in addition to supportive and antibiotic therapy. ⋯ Mortality from infection in 'culture proven sepsis' was 3/44 (6.8%) in the IgM-enriched IVIG group, 6/42 (14.2%) in the standard IVIG group, and 11/43 (25.5%) in the control group (P = 0.017, IgM versus control, P = 0.19 standard IVIG versus control). There was no statistical difference in the outcome between the two immunoglobulin therapy groups (P = 0.25). The study indicates that IVIG improves outcome in neonatal sepsis when used as an adjunct to supportive and antibiotic therapy, but larger studies are required to confirm this.