Rhinovirus replication causes RANTES production in primary bronchial epithelial cells.

The mechanisms by which rhinovirus (RV) infections produce lower airway symptoms in asthmatic individuals are not fully established. To determine effects of RV infection on lung epithelial cells, primary human bronchial epithelial (BE) cells were infected with either RV16 or RV49, and viral replication, cell viability, and cell activation were measured. Both viral serotypes replicated in BE cells at 33 degrees C (DeltaTCID50 / ml = 2 to 2.5 log units) and at 37 degrees C (DeltaTCID50 /ml = 1.6 log units), but only high doses of RV49 (10(6) TCID50 /ml) caused cytopathic effects and reduced cell viability. In addition, regulated on activation, normal T cells expressed and secreted (RANTES) secretion was increased in epithelial cells infected with RV16 or RV49 (243 and 398 pg/ml versus 13 pg/ml uninfected control cells), and a similar pattern was seen for RANTES messenger RNA. RV infection also caused increased secretion of interleukin-8 and granulocyte macrophage colony-stimulating factor, but did not alter expression of either intercellular adhesion molecule-1 or human leukocyte-associated antigen-DR. These observations suggest that RVs can replicate in lower airway cells in vivo, and support epidemiologic studies that link RV with lower respiratory illnesses. Further, RV-induced secretion of RANTES and other cytokines could trigger antiviral immune responses in vivo, but these effects could also contribute to the pathogenesis of respiratory symptoms in subjects with asthma.

Meperidine attenuates the secretion but not the transcription of interleukin 1 beta in human mononuclear leukocytes.

BACKGROUND: The infusion of amphotericin-B (AmB) often produces clinically distressing rigors and chills, which promptly abate with intravenous injection of meperidine, although its mechanism of action is unknown. OBJECTIVE: To examine the effects of meperidine on the transcription or secretion of Interleukin 1 beta (IL-1 beta) in human mononuclear leukocytes (MNL) exposed in vitro to the lipopolysaccharide (LPS) contained in Escherichia coli endotoxin or to AmB. METHODS: Blood was drawn from eight healthy adult volunteers. The blood was centrifuged, and the layer containing MNL was separated; incubated with various combinations of medium, meperidine, and AmB; then tested for IL-1 content to determine the effect of meperidine on MNL secretion of IL-1 beta. To determine the effect on MNL transcription of IL-1 beta, the RNA was extracted from cells and the IL-1 beta was measured using one of two different methods. RESULTS: Incubation of human MNL in the presence of LPS or AmB significantly increased transcription of IL-1 beta mRNA and secretion of IL-1 beta. Addition of meperidine to these cultures significantly reduced LPS-induced, but not AmB-induced, secretion of IL-1 beta in vitro. Meperidine did not alter IL-1 beta mRNA levels in MNL exposed to LPS or AmB. CONCLUSIONS: These data suggest that meperidine decreases rigors and chills in part by decreasing MNL secretion of IL-1 beta through a posttranscriptional mechanism.

Detection of rhinovirus RNA in lower airway cells during experimentally induced infection.

Rhinovirus (RV) infections are presumed to be localized to the upper airway, yet can cause severe lower airway symptoms in children and adults with asthma. To test the hypothesis that rhinovirus infection of the upper airway may be associated with the presence of virus in lower airway cells, we used the techniques of reverse transcription-polymerase chain reaction (RT-PCR) and Southern blotting to detect RV RNA in lower airway cells from eight allergic volunteers experimentally infected with RV16. Bronchoscopy with bronchoalveolar lavage (BAL) was done 1 mo before, and 2 and 4 d after an experimental infection with RV16. All subjects developed cold symptoms, and infection was confirmed by culturing RV16 from nasal secretions. Rhinovirus RNA was detected in both nasal lavage and lower airway cells from all eight subjects 2 to 4 d after an experimental inoculation, but not in any of the precold specimens from either the nose or the lower airway. These findings suggest that RV can infect cells of the lower airway, and raise the possibility that such an effect can promote asthma exacerbations in the susceptible host through direct enhancement of local inflammation.

Rhinovirus inhibits antigen-specific T cell proliferation through an intercellular adhesion molecule-1-dependent mechanism.

To determine whether binding of human rhinovirus (HRV) to intracellular adhesion molecule-1 might disrupt airway immune processes, effects of a major HRV group, HRV-16, on T cell proliferation and cytotoxicity were defined. HRV (1-10 TCID50/cell) significantly inhibited T cell proliferation induced by antigen but not proliferation secondary to mitogens, interleukin-2, or an irradiated allogeneic T cell line. Noninfectious (UV-irradiated) HRV had similar effects. Inhibition of T cell proliferation was dependent on HRV binding to intercellular adhesion molecule-1 on monocytes, indicating that the virus interferes with lymphocyte activation indirectly through effects on antigen-presenting cells. In addition, HRV inhibited T cell cytotoxic responses but not NK cell activity. If these effects also occur in vivo, the resulting disturbance in local airway immunity could increase the chances of successful viral replication, and might also be a factor in the pathogenesis of secondary viral or bacterial respiratory tract infections.