Koji Shirotori

The effect of recombinant human interleukin-5 on eosinophil accumulation and degranulation in human nasal mucosa

Recombinant human interleukin-5 (rhIL-5) was administered repeatedly onto the nasal mucosa of individuals with Japanese cedar pollinosis outside the pollen season. The numbers of eosinophils and epithelial cells and the amount of eosinophil cationic protein (ECP), secretory IgA (S-IgA), and IgA in the nasal lavage fluid increased significantly after the application of rhIL-5. Responsiveness to histamine was also enhanced after the application. When S-IgA was administered onto the nasal mucosa after application of rhIL-5, the amount of ECP in the nasal lavage fluid was significantly more increased. The above findings together with the facts that IL-5 promotes production of IgA, that IgA receptors are present on eosinophils, and that rhIL-5 does not increase release of ECP from eosinophils isolated from the peripheral blood suggest that a series of possible reactions consisting of (1) IL-5--induced production of IgA from the immune-mediating cells, (2) binding of secretory components released from either serous glandular cells or epithelial cells of the nasal mucosa with IgA, (3) release of ECP from eosinophils induced by S-IgA and/or IgA, (4) epithelial damage to the nasal mucosa, and (5) development of nasal hyperreactivity to histamine.

Mechanism of eosinophil infiltration in the patient with subcutaneous angioblastic lymphoid hyperplasia with eosinophilia (Kimura's disease). Mechanism of eosinophil chemotaxis mediated by candida antigen and IL-5.

Kimuras disease is a chronic granulomatous disease of unknown etiology. Although eosinophilia is one of the characteristic features in this disease, little is known about the mechanism of eosinophilia. In the present study it was demonstrated that interleukin-5 (IL-5) was produced and released from the site of a granuloma and lymph nodes after stimulation with candida antigen. It was also shown that peripheral blood eosinophils from patients with Kimuras disease contained a large proportion of hypodense eosinophils and that their viability was prolonged. These results strongly suggest that locally produced IL-5 induced by candida antigen contributes to the eosinophilia in this disease.

Detection of genomic sequences of respiratory syncytial virus in otitis media with effusion in children.

The reverse transcriptase—polymerase chain reaction and the nested polymerase chain reaction were used for detection of respiratory syncytial virus (RSV) sequences in middle ear effusions collected from children with otitis media. Sequences of RSV were detected in 21 of 34 samples tested. These samples were collected during and/or after natural outbreaks of RSV infection in the community. In those patients from whose nasopharynges RSV was isolated, the viral sequences were highly detectable (75%) in the effusions. These observations suggest RSV as an important factor in the pathogenesis of otitis media with effusion.

Interleukin-5 Gene Expression in Nasal Mucosa and Changes in Amount of Interleukin-5 in Nasal Lavage Fluid After Antigen Challenge

Eosinophils and their products are known to cause hyperreactivity and swelling of the nasal mucosa in subjects with nasal allergy. Interleukin-5 (IL-5) not only induces differentiation and proliferation of immature eosinophils but also causes mature cells to accumulate and activate. This study shows that IL-5 is actually produced in the human nasal mucosa by antigen challenge, and it further investigates the changes in the amount of IL-5 in nasal lavage fluids after antigen challenge. Expression of mRNA for IL-5 in nasal mucosa was investigated using the reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis. Among the 4 subjects with nasal allergy examined in this study, expression of mRNA for IL-5 was observed in 2 prior to antigen challenge; within 6 h after antigen challenge it was seen in 3 subjects. We also found that the amount of IL-5 in the nasal lavage fluids obtained consecutively after antigen challenge increased predominantly in the late phase, and that the number of eosinophils in the IL-5 positive group was significantly higher than that in the IL-5 negative group. These results strongly suggest that IL-5 contributes to the recruitment of eosinophils in the nasal mucosa of the subjects with nasal allergy.

Changes in nasal responsiveness to histamine and to specific antigen after laser surgery.

An initial treatment with several kinds of anti-allergic medicines is useful for reducing nasal allergy symptoms in patients suffering from Japanese cedar pollinosis during the pollen season. Since laser surgery before the pollen season seems to have a preventive effect as well, it would be of interest to know the time course of changes in the nasal reactivity to specific and non-specific stimuli after laser surgery. In this study, we investigated the changes in the nasal reactivities to specific antigen and histamine after CO2 laser surgery. The nasal reactivities to both specific antigen and histamine were enhanced 2 weeks after the laser surgery. On the other hand, they were significantly reduced after 4 weeks. Our data strongly suggest. therefore. that laser surgery must be done more than 4 weeks before the start of the pollen season to avoid temporary enhancement of nasal allergy symptoms.

The Influence of RS Viral Infection on the Development of Otitis Media with Effusion

The polymerase chain reaction was used for detection of RS viral sequences in middle ear effusion collected from children with otitis media. RS viral sequences were detected in 21 out of 34 samples tested These sample were collected during and/or the after natural outbreak of RSV infection in the community. The viral sequences were highly detectable (85.7%) in the effusions of the patients from whom the nasopharynx RSV was isolated. On the other hand, several immunoregulatory cytokines were present in the ME effusions during RSV infection and in vitro mucosal RSV infection up-regulated production of certain cytokines, paticularly those with inflammatory properties. These observations suggest that RSV is an important factor in the pathogenesis of otitis media with effusion and that exaggerated production of cytokines in association with RSV infection may lead to the development of infection-induced inflammation, and effusion.