Kou Uchida

Role of interferon-gamma in inflammatory responses in murine respiratory infection with Legionella pneumophila.

The role of interferon (IFN)-gamma in host inflammatory responses, including inflammatory cytokine production, in experimental pneumonia with Legionella pneumophila was examined in IFN-gamma knockout (IFN-gamma-/-) mice. IFN-gamma-/- mice and wild-type BALB/cA mice were inoculated intranasally with L. pneumophila strain KC. The survival rate of IFN-gamma-/- mice was significantly lower than that of control mice. Viable bacterial counts in lungs and blood showed a rapid and continuous increase in IFN-gamma-/- mice, in contrast to a gradual decrease in the lungs and an intermittent bacteraemia in control mice. Histopathological analysis of L. pneumophila-infected lung tissues demonstrated mild pneumonia in control mice, whereas severe pneumonia was shown in IFN-gamma-/- mice. During the late stages of infection, the number of total bronchoalveolar lavage (BAL) cells was significantly higher in IFN-gamma-/- than in control mice. The concentrations of tumour necrosis factor-alpha and interleukin-1beta in sera of IFN-gamma-/- mice were significantly lower in control mice during the early stages of infection, suggesting suppressed production of inflammatory cytokines in IFN-gamma-/- mice. In contrast, during the late stages of infection, the levels of these cytokines were significantly higher in sera of IFN-gamma-/- mice than in control mice, suggesting severe and systemic infection in IFN-gamma-/- mice. The findings suggest that retardation of host immune responses, including inflammatory cytokine production caused by deficiency of IFN-gamma, might allow the bacteria to grow and cause fulminant pneumonia.

Role of bacterial capsule in local and systemic inflammatory responses of mice during pulmonary infection with Klebsiella pneumoniae.

The role of bacterial capsule in inflammatory responses in experimentally induced pneumonia caused by Klebsiella pneumoniae was evaluated by comparing the host immunological responses in mice infected with capsulate strain DT-S and non-capsulate mutant strain DT-X. Anaesthetised ICR mice were infected intranasally with inocula of strain DT-S or DT-X. Mice infected with strain DT-X survived significantly longer than those inoculated with strain DT-S. Viable bacterial counts in lungs and blood increased rapidly in mice infected with strain DT-S, in contrast to the gradual decrease in their density in lungs and intermittent bacteraemia in mice infected with strain DT-X. The number of broncho-alveolar lavage (BAL) cells in mice infected with strain DT-X at 24 h after inoculation was significantly higher than in those infected with strain DT-S. In the early stages of infection, the levels of tumour necrosis factor-a and interleukin-6 in BAL fluid of mice infected with strain DT-X were significantly higher than those of mice infected with strain DT-S. In contrast, in the late stage of infection, the levels of these cytokines in serum of mice infected with strain DT-S were significantly higher than in mice infected with strain DT-X. These results suggest that K. pneumoniae capsule may suppress the host immunological responses,thus allowing the bacteria to grow, causing pneumonia, septicaemia and death.

Induction of interleukin-10 and down-regulation of cytokine production by Klebsiella pneumoniae capsule in mice with pulmonary infection.

The role of the capsule of Klebsiella pneumoniae in inducing cytokine production was investigated by comparing the responses of mice with experimentally induced pneumonia caused by capsulate (strain DT-S) or non-capsulate (mutant strain DT-X) K. pneumoniae. Anaesthetised ICR mice were inoculated intranasally. Whereas all DT-S-infected mice died within 3 days, no deaths were observed in DT-X-infected mice by 14 days after infection. During the early stage of infection, interferon-gamma (IFN-gamma) levels in bronchoalveolar lavage fluid (BALF) of DT-X-infected mice were significantly higher than those in DT-S-infected mice. In contrast, in the late stage of infection, serum levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and IFN-gamma in DT-S-infected mice were significantly higher than those in DT-X-infected mice. Levels of interleukin10 (IL-10) in BALF and serum of DT-S-infected mice were significantly and persistently higher than those of DT-X-infected mice. The IL-10/TNF-alpha (tumour necrosis factor-a) ratios in BALF and serum indicated that higher levels of IL-10 production were induced in mice infected with strain DT-S than in those infected with strain DT-X. The results suggest that the capsule of K. pneumoniae may induce IL-10 production at the site of infection and, thereafter, these high IL-10 levels may serve to down-regulate the expression of pro-inflammatory cytokines.

Protection against pulmonary infection with Klebsiella pneumoniae in mice by interferon-γ through activation of phagocytic cells and stimulation of production of other cytokines

The study was designed to determine the role of interferon (IFN)-gamma in inflammatory responses against experimentally induced pneumonia caused by Klebsiella pneumoniae. The host immunological responses in IFN-gamma gene knockout (IFN-gamma(-/-)) mice and immunocompetent control mice were compared. K. pneumoniae strain T-113 was inoculated intranasally into anaesthetised mice to induce pneumonia. Infected control mice survived significantly longer than infected IFN-gamma(-/-) mice. Viable bacterial counts in lungs and blood abruptly increased in IFN-gamma(-/-) mice; in contrast, a gradual decrease in the number of bacteria was noted in control mice. During the early stages of infection, the concentrations of interleukin (IL)-1beta and IL-6 in broncho-alveolar lavage fluid and IL-1beta in serum of IFN-gamma(-/-) mice were significantly lower than in control mice. During the late stage of infection, serum IL-6 level in IFN-gamma(-/-) mice was significantly higher than in control mice. These results suggest that the defective immunological host response, including inflammatory cytokine production caused by deficiency of IFN-gamma, is one of the mechanisms that allow the progression of pulmonary infection to systemic septicaemia.

A case of pulmonary arteritis with stenosis of the main pulmonary arteries with positive myeloperoxidase-antineutrophil cytoplasmic autoantibodies

A 53‐year‐old woman was referred to our hospital with the main symptoms of productive cough, fever and exertional dyspnoea. Chest X‐ray revealed enlargement of the left hilar shadow and cavitary infiltration in the right upper lobe. 99mTechnetium‐macroaggregated albumin (99mTc‐MAA) perfusion scintigram showed complete hypoperfusion through the entire right lung. A pulmonary angiogram revealed stenotic lesions in the right and left main pulmonary arteries. Right cardiac catheterization showed an elevated right ventricular systolic pressure. There was no evidence of systemic arterial lesions nor vasculitis. The patient was positive for myeloperoxidase (MPO)antineutrophil cytoplasmic autoantibodies (ANCA) (168 EU). The Mycobacterium avium complex sputum culture was positive. The pulmonary stenotic lesions were surgically resected. The resected pulmonary arterial lesions were pathologically diagnosed as non‐specific vasculitis. The cavitary lesion disappeared 6 months after the surgery. Two years after the surgery, although the MPO‐ANCA level had decreased to 12 EU, stenosis of the pulmonary arteries reappeared. It is suggested that the patient became positive for MPO‐ANCA in association with the Mycobacterium avium complex infection, and that the presence of MPO‐ANCA may not be related to the development of pulmonary stenosis of the main pulmonary arteries.

Ventilation-perfusion scintigram in diabetics

We carried out ventilation and perfusion scintigraphies and pulmonary function tests in 20 diabetics under 50 years of age.99mTc-MAA perfusion scintigrams showed evidence of minimal nonuniformity (MNU) in four cases (20 %) and nonsegmental defect (NSD) in eight cases (40%). There was a ventilation defect in the single-breath image in one case (5%) and a delayed washout in three cases (15%) upon133Xe ventilation scintigram. In the NSD group, the mean diffusing capacity value was abnormally low and the mean duration of the diabetes was long compared with other groups. The frequency of perfusion defects was higher than that of ventilation abnormalities ; moreover, abnormal findings on ventilation scintigrams were very mild compared with those of perfusion defects. Perfusion defects correlated significantly with a decrease in diffusing capacity. These findings suggest that the disturbance in pulmonary arterial perfusion caused a decrease in diffusing capacity in diabetics.

A case of Legionella pneumophila pneumonia complicated by miliary tuberculosis.

A 47‐year‐old woman was admitted to hospital with severe Legionella pneumonia. The respiratory symptoms improved dramatically and the X‐rays revealed a decrease in the diffuse chest infiltrates after treatment with erythromycin and rifampicin. However, chest CT scans showed that the reticulonodular opacities persisted for several weeks after the onset of pneumonia. Two months after admission, the chest X‐rays showed the progression of small nodules in both lungs and there was increasing respiratory distress. A diagnosis of miliary tuberculosis was confirmed. The present case should alert physicians to this potentially confusing combination of respiratory pathogens.

USEFULNESS OF AROUSAL FOR THE DIAGNOSIS OF SLEEP BREATHING DISORDER

Abstract We hypothesize that breathing disorder related arousal index (B‐ArI) can differentiate sleep breathing disorder from simple snorer when apnea hypopnea index (AHI) is low. We studied 54 patients using polysomnography. Breathing disorder related arousal (B‐Ar) was defined as arousal accompanied by apnea, hypopnea, desaturation or snort. Mean AHI was 44.2 ± 34.0/h, and B‐ArI correlated significantly with AHI, desaturation index, percentage total sleep time with SpO2 below 90%. Breathing disorder related arousal index was greater than AHI when AHI was below 20. In 11/54 patients, AHI was below 10, and B‐ArI more than 10. Nasal continuous positive airway pressure was applied to six patients and showed reduced B‐ArI. Breathing disorder related arousal index may be one of the useful indices for the diagnosis of sleep breathing disorder when AHI is less than 10.