The effects of vitamin A supplementation with measles vaccine on leucocyte counts and in vitro cytokine production.

As WHO recommends vitamin A supplementation (VAS) at vaccination contacts after age 6 months, many children receive VAS together with measles vaccine (MV). We aimed to investigate the immunological effect of VAS given with MV. Within a randomised placebo-controlled trial investigating the effect on overall mortality of providing VAS with vaccines in Guinea-Bissau, we conducted an immunological sub-study of VAS v. placebo with MV, analysing leucocyte counts, whole blood in vitro cytokine production, vitamin A status and concentration of C-reactive protein (CRP). VAS compared with placebo was associated with an increased frequency of CRP ≥ 5 mg/l (28 v. 12%; P=0·005). Six weeks after supplementation, VAS had significant sex-differential effects on leucocyte, lymphocyte, monocyte and basophil cell counts, decreasing them in males but increasing them in females. Mainly in females, the effect of VAS on cytokine responses differed by previous VAS: in previous VAS recipients, VAS increased the pro-inflammatory and T helper cell type 1 (Th1) cytokine responses, whereas VAS decreased these responses in previously unsupplemented children. In previous VAS recipients, VAS was associated with increased IFN-γ responses to phytohaemagglutinin in females (geometric mean ratio (GMR): 3·97; 95% CI 1·44, 10·90) but not in males (GMR 0·44; 95% CI 0·14, 1·42); the opposite was observed in previously unsupplemented children. Our results corroborate that VAS provided with MV has immunological effects, which may depend on sex and previous VAS. VAS may increase the number of leucocytes, but also repress both the innate and lymphocyte-derived cytokine responses in females, whereas this repression may be opposite if the females have previously received VAS.

Hyperthermic pre-conditioning promotes measles virus clearance from brain in a mouse model of persistent infection.

Nervous tissue subjected to hyperthermic pre-conditioning is resistance to numerous insults although in vitro, the same treatment can increase gene expression and cytopathic effect of neurotropic paramyxoviruses, including measles virus (MV). The present work determined whether the in vivo relationship between hyperthermic pre-conditioning and MV infection would be to increase neuropathogenicity or, conversely, to promote clearance. Balb/c mice 36 h of age were exposed to a 41 degrees C hyperthermic treatment for 30 min. Intracranial inoculation of mice with Edmonston MV was performed at 6 h following the heat treatment, a time point exhibiting elevated levels of the major inducible 70-kDa heat shock protein in brain, a hallmark of pre-conditioning. Forty-seven percent of the non-heated animals supported a persistent cytopathic infection at 21-day post infection (PI) based upon the quantitative detection of viral RNA in brain using real time RT-PCR. Cytopathic effect in the infected brains was proportionate to viral RNA burden. In contrast, infected stress conditioned mice lacked significant cytopathic effect and clearance was demonstrated in 95% of the animals. Analysis of shorter post-infection intervals showed that levels of viral RNA in brain were equivalent between stress conditioned and non-conditioned mice at 2 and 7 days PI, with clearance being first evident in both groups at 14 days. The temporal onset and progression of clearance was correlated to splenocyte blastogenic responsiveness to purified MV antigen but not the production of MV-specific antibody. Collectively, these results support the hypothesis that stress conditioning enhances the efficacy of cell-mediated immune responses known to mediate viral clearance from brain.

A low molar ratio of retinol binding protein to transthyretin indicates vitamin A deficiency during inflammation: studies in rats and a posterior analysis of vitamin A-supplemented children with measles.

To assess whether the molar ratio of retinol-binding protein (RBP) to transthyretin (TTR) is of utility in detecting vitamin A (VA) deficiency during inflammation, we analyzed data from a rat model of endotoxin-induced inflammation and from a previously reported randomized, placebo-controlled trial of VA supplementation in children with acute measles. In rats, both marginal VA deficiency and inflammation were independent causes of low plasma RBP (two-way ANOVA, P < 0.001), whereas plasma TTR concentration was reduced only by inflammation (P < 0.001). The molar ratio of plasma RBP to TTR was reduced (by approximately 50%) only in rats with marginal VA deficiency and inflammation (two-way ANOVA interaction, P < 0.01). Serum retinol concentration, C-reactive protein (CRP, an indicator of inflammation) and the RBP:TTR molar ratio were determined in children with acute measles at baseline and 2 wk after subgroups received a placebo or a 210 micromol VA supplement. The ratio of RBP:TTR was selectively reduced in children in the placebo group with low plasma retinol (<0.35 micromol/L) and elevated CRP (>40 mg/L). In children with a low RBP:TTR molar ratio (<0.30) at baseline, the RBP:TTR ratio increased significantly 2 wk later only in the VA-treated subgroup. These analyses provide evidence that, because RBP is differentially reduced in comparison to TTR during VA deficiency, the combined determination of the concentrations of serum RBP and TTR may provide a promising means of detecting VA deficiency during inflammation.

Urinary riboflavin excretion and erythrocyte glutathione reductase activity in preschool children suffering from upper respiratory infections and measles.

The urinary and blood levels of riboflavin and erythrocyte glutathione reductase (EGR) activity and its stimulation with FAD (EGR-AC) were examined in preschool children suffering from either measles or other upper respiratory infections and matched controls. Patients showed significantly higher levels of urinary riboflavin (per unit creatinine), erythrocyte riboflavin and EGR activity and lower EGR-AC values. This trend reversed after treatment. Mobilization of riboflavin from a labile tissue pool during infections may produce artefactual changes in the biochemical indices of riboflavin status. It would also prevent tissue saturation despite supplementation.