Treatment of the common cold with troxerutin.

The rutosides are naturally occurring flavonoids that have documented effects on capillary permeability and edema. The purpose of this study was to assess the effect of troxerutin, one of the rutosides, on the symptoms of the common cold. Ninety-four volunteers with common cold symptoms were recruited for participation in the study. Volunteers were randomized to either active treatment (n=49) with troxerutin (50 mg) and Zn gluconate (25 mg) or control treatment (n=45) with 10 mg Zn gluconate. Symptoms were assessed by subjective symptom score prior to treatment and then daily for the next 4 days. The total symptom score over the 4 days of study treatment was 27.7+/-2.0 (mean+/-SEM) and 33.0+/-2.6 in the active and control groups, respectively (p=0.10, unpaired t-test). The total daily symptom score on day 1 was reduced by 11% compared to baseline in the active group and by 1% in the control group (p=0.03). Evaluation of the effect of treatment on individual symptoms revealed a significant effect on rhinorrhea. The total rhinorrhea score over the course of the study was 3.7+/-0.4 in the active group compared to 5.1+/-0.5 in the control group (p=0.025, unpaired t-test). Daily rhinorrhea scores were significantly lower in the active group on study days 1 and 3. Based on this preliminary study, the possibility that the rutosides might provide a safe and effective treatment for rhinorrhea in the common cold deserves systematic evaluation.

The regulation of rhinovirus infection in vitro by IL-8, HuIFN-alpha, and TNF-alpha.

The influence of three important cytokines (IL-8, TNF-alpha, and HuIFN-alpha) on ongoing rhinovirus infections has been examined in vitro, individually or as combinations. TNF-alpha was able to transform traces of HRV infections into full-blown infections. Furthermore, TNF-alpha was able to down-regulate the antiviral action of HuIFN-alpha completely, even at levels of just a few pg/ml. This suggests that the induction of TNF-alpha by HRV may be part of the virus's strategy to minimize the interferon response which is part of the host's immune defence system. However, troxerutin (a flavonoid) was able to neutralize the downregulatory action of TNF-alpha on the HuIFN-alpha system at low levels and re-establish the antiviral activity ascribed to IFN-alpha. IL-8 exerted a minor influence on the interferon system, and had no influence on rhinovirus infections. The in vitro findings are supported, in part, by recent in vivo findings in a common cold pilot study.

Measles virus-induced modulation of host-cell gene expression.

The influence of measles virus (MV) infection on gene expression by human peripheral blood mononuclear cells (PBMCs) was examined with cDNA microarrays. The mRNA levels of more than 3000 cellular genes were compared between uninfected PBMCs and cells infected with either the Edmonston MV strain or a wild-type MV isolate. The MV-induced upregulation of individual genes identified by microarray analyses was confirmed by RT-PCR. In the present study, a total of 17 genes was found to be upregulated by MV infection. The Edmonston strain grew better in the PBMC cultures than the wild-type MV, and the Edmonston strain was a stronger inducer of the upregulated host cell genes than the wild-type virus. The anti-apoptotic B cell lymphoma 3 (Bcl-3) protein and the transcription factor NF-kappaB p52 subunit were upregulated in infected PBMCs both at the mRNA and at the protein level. Several genes of the interferon system including that for interferon regulatory factor 7 were upregulated by MV. The genes for a number of chaperones, transcription factors and other proteins of the endoplasmic reticulum stress response were also upregulated. These included the gene for the pro-apoptotic and growth arrest-inducing CHOP/GADD153 protein. Thus, the present study demonstrated the activation by MV of cellular mechanisms and pathways that may play a role in the pathogenesis of measles.