We examined the effects of interleukin-8 (IL-8) on cytomegalovirus (CMV) replication in human fibroblasts. Exposure of fibroblasts to IL-8 augmented both infectious virus production and replication of CMV, with concomitant increases in the levels of both the transcript of the CMV pp7l genome and the synthesis of the CMV late antigen. We also found that CMV selectively induced transcripts of the IL-8 type 1 receptor in fibroblasts. These results suggest that IL-8 also contributes to inflammatory diseases by enhancing CMV replication and that CMV regulates its production through induction of the IL-8 receptor.
To analyze persistent infection by human cytomegalovirus (HCMV) in vivo, specimens obtained from various sources and autopsied organs were examined for the presence of HCMV DNA, mRNA transcripts and antigens by polymerase chain reaction, in situ hybridization and immunostaining. The HCMV genome was detected in lung, liver, kidney, and blood vessels at an average positive rate of 15%. The highest PCR-positive rate was observed with cervical smears. Subsequent examination of uterus tissues from patients with myoma revealed HCMV transcripts and antigens in glandular epithelial cells, leukocytes, endothelial cells, and others, indicating productive HCMV infection of cervical tissue.
Synovial fluid aspirated from 34 patients with symptomatic rheumatoid arthritis (RA) was evaluated for the presence of human cytomegalovirus (CMV) genomic material using polymerase chain reaction (PCR), and for levels of interleukin 8 (IL-8) and IL-6 using enzyme-linked immunoadsorbence assay. IL-8 and IL-6 levels were significantly higher in CMV DNA-positive RA patients than CMV DNA-negative RA patients and at least 10-fold higher than in both corresponding control groups of patients with osteoarthritis (OA). These findings suggest an association between elevated IL-8 and IL-6 levels and the presence of the CMV genome in RA patients.
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