Martha L. Warnock

IL-13 and IFN-γ: Interactions in Lung Inflammation

Chronic inflammatory diseases of the lungs, such as asthma, are frequently associated with mixed (Th2 and Th1) T cell responses. We examined the impact of critical Th1 and Th2 cytokines, IFN-γ and IL-13, on the responses in the lungs. In a mouse model of airway inflammation induced by mixed T cell responses, the number of Th1 (IFN-γ-positive) cells was found to be negatively correlated with airway hyperreactivity. In these mice, blockade of IL-13 partially inhibited airway hyperreactivity and goblet cell hyperplasia but not inflammation. In contrast, in mice that responded with a polarized Th2 response to the same Ag, blockade of IL-13 inhibited airway hyperreactivity, goblet cell hyperplasia, and airway inflammation. These results indicated that the presence of IFN-γ would modulate the effects of IL-13 in the lungs. To test this hypothesis, wild-type mice were given recombinant cytokines intranasally. IFN-γ inhibited IL-13-induced goblet cell hyperplasia and airway eosinophilia. At the same time, IFN-γ and IL-13 potentiated each other’s effects. In the airways of mice given IL-13 and IFN-γ, levels of IL-6 were increased as well as numbers of NK cells and of CD11c-positive cells expressing MHC class II and high levels of CD86. In conclusion, IFN-γ has double-sided effects (inhibiting some, potentiating others) on IL-13-induced changes in the lungs. This may be the reason for the ambiguous role of Th1 responses on Th2 response-induced lung injury.

Assessment of lungs rejected for transplantation and implications for donor selection

Present criteria for donor-lung selection exclude more than 85% of lungs. We aimed to establish if potentially suitable lungs are rejected for transplantation. We obtained 29 pairs of rejected lungs and assessed them by physiological, microbiological, and histological methods. Most donor lungs had no or mild pulmonary oedema (24/29 [83%]), intact alveolar fluid clearance (17/23 [74%]), and normal or mildly abnormal histological findings (18/29 [62%]). When all factors were considered, including microbiological and non-lung donor factors, 12 (41%) of 29 pairs of rejected lungs would have been potentially suitable for transplantation. Our findings emphasise the urgent need for prospective scientific assessment of selection of donors for lung transplantation.

Severe pulmonary hypertension and cor pulmonale in the acquired immunodeficiency syndrome

Abstract Numerous cardiopulmonary manifestations of the acquired immunodeficiency syndrome (AIDS) have been reported. 1,2 We have previously found that dilated cardiomyopathy, pericardial effusion and pleural effusion are the most common cardiopulmonary lesions detected by echocardiography in hospitalized AIDS patients. 3 We have also noted evidence of mild to moderate pulmonary hypertension in patients with dilated cardiomyopathy and occasional patients with active Pneumocystis carinii pneumonia. 3 By necropsy studies, some AIDS patients with Pneumocystis carinii pneumonia or cytomegalovirus infection of the lung have had right ventricular dilatation in the absence of left ventricular dilatation or myocarditis. 2 Although pulmonary emboli, pulmonary infarction, venous thromboemboli and non-bacterial thrombotic endocarditis have also been demonstrated by autopsy in AIDS patients, cor pulmonale has not been reported previously.

Pulmonary veno-occlusive disease after chemotherapy

A case of pulmonary veno-occlusive disease (PVOD) in a 41-year-old woman who had received chemotherapy (bleomycin, mitomycin-C, and cis-platinum) for metastatic cervical carcinoma is reported. Before her death, pulmonary hypertension and right ventricular heart failure had been attributed to lung toxicity induced by chemotherapy, but the postmortem findings were characteristic of PVOD. The authors support the view that PVOD is a syndrome, not a distinct entity, and present the case as a further example of the many situations in which PVOD can arise. Whether the lesions of the pulmonary veins developed as a result of the chemotherapy or whether the two conditions were associated by chance must remain, for now, a subject of speculation. Pathologists are urged to devote special attention to the examination of the pulmonary vessels in patients who have received chemotherapy.

Further observations on cytoplasmic hyaline in the lung

Cytoplasmic hyaline material resembling Mallorys alcoholic hyaline has previously been described in pulmonary alveolar cells of patients with asbestosis. We present 14 new cases of cytoplasmic hyaline found in patients with a variety of processes causing damage to the alveolar lining; these include cases of radiation pneumonia, diffuse interstitial fibrosis, organizing bacterial pneumonia, as well as asbestosis. Hyaline was found only in the setting of an unusual type II cell change, which ultrastructurally appeared to represent squamous metaplasia. We conclude that pulmonary cytoplasmic hyaline is not specific for asbestosis but rather is a nonspecific reaction to injury;

Asbestos bodies or fibers and the diagnosis of asbestosis

A committee of the College of American Pathologists has proposed that the diagnosis of asbestosis requires fibrosis in respiratory bronchiolar walls and the presence of asbestos bodies (ABs) in tissue sections. To determine whether histologic ABs reliably reflect asbestos fiber concentrations in asbestosis, we compared the concentration of ABs in histologic sections to concentrations of ABs and fibers in tissue extracts of 14 asbestos workers with nonspecific interstitial fibrosis. ABs in histologic sections and extracts correlated well, r = 0.95. Counted and classified by electron microscopy, electron diffraction, and X-ray spectroscopy, commercial amphibole fibers (r = 0.94) also correlated well with ABs, but noncommercial amphiboles (r = -0.02) or chrysotile (r = 0.29) did not. In five subjects with a high percentage of noncommerical amphibole fibers, fewer than 0.5 histologic ABs/cm2 were present despite a total amphibole concentration that was similar to that in subjects with more histologic ABs. We conclude that ABs will be scarce or absent in histologic sections from some subjects with asbestosis, and that for such subjects, extracts of asbestos fibers should yield over 500,000 total amphibole fibers/g dry lung to signify that interstitial fibrosis may be caused by asbestos.

Hard metal interstitial lung disease: high-resolution computed tomography appearance.

Hard metal interstitial lung disease (HM-ILD) is a rare form of interstitial lung disease caused by aerosolized particulates containing cobalt inhaled during the manufacture or grinding of hard metal. The high-resolution computed tomography (HRCT) appearance of HM-ILD includes reticulation, traction bronchiectasis, and large peripheral cystic spaces in a mid and upper lung distribution. This appearance, along with a consistent occupational exposure, should specifically suggest the diagnosis of HM-ILD.

Use of the polymerase chain reaction in the diagnosis of unsuspected herpes simplex viral pneumonia: Report of a case

A 30-year-old apparently immunocompetent woman presented with acute respiratory failure (acute respiratory distress syndrome). No etiologic agent was found, and she died 2 weeks later despite antibiotic therapy. Postmortem examination of the lungs showed diffuse organizing alveolar damage with superimposed focal necrotizing peribronchiolar pneumonia. Cultures obtained from lung tissue were negative for virus, fungi, and bacteria. Histopathologic and electron microscopic studies showed that the necrotizing changes were consistent with herpesvirus infection. With the use of a new diagnostic tool, the polymerase chain reaction, a specific diagnosis of herpes simplex virus pneumonia was made, and other viral agents were excluded. The polymerase chain reaction is a sensitive, specific, and rapid technique that may greatly facilitate establishing an infectious etiology in cases of pneumonia.

Primary pulmonary hypertension and human immunodeficiency virus infection in a non-hemophiliac man

We describe clinical and postmortem findings in a 44-year-old man with pulmonary hypertension and infection with the human immunodeficiency virus (HIV-1). Plexogenic angiopathy and veno-occlusive lesions were present, in addition to a mild, patchy pulmonary interstitial lymphoid infiltrate. The clinical data for 14 previously reported cases of HIV-associated primary pulmonary hypertension are summarized. We speculate that these vascular changes may be due to damage from a specific immune response to HIV.

Lung asbestos burden in shipyard and construction workers with mesothelioma: comparison with burdens in subjects with asbestosis or lung cancer

Although mesothelioma is generally considered to be caused by asbestos, epidemiologic studies indicate that some cases have another cause. In order to determine whether pulmonary asbestos burden can be used to define asbestos-related mesotheliomas, asbestos burden was quantified in 27 shipyard or construction workers with diffuse malignant mesothelioma of the pleura or peritoneum and a history of asbestos exposure. Their burden was significantly greater than the burden found in 19 unexposed men (P less than 0.001). The burdens were also compared to those of previously reported subjects with asbestosis or lung cancer. The median concentration for total amphibole fibers (2.7 million/g dry lung) in subjects with mesothelioma did not differ significantly from our previously reported median values for 14 subjects with asbestosis (1.3 million/g dry lung) or for 60 asbestos workers with lung cancer (1.3 million/g dry lung). Fiber size distribution for amosite, the most prevalent fiber type, was similar in all three subject groups. Fifteen of 25 (60%) subjects with mesothelioma had mild asbestosis. Asbestos body (AB) concentrations were greater than or equal to 1900/g dry lung, and total amphibole fiber concentrations were greater than or equal to 390,000/g dry lung. Counts of ABs greater than or equal to 0.5/cm2 in histologic sections always signified both of these concentrations in extracts. Thus, histologic sections showing greater than or equal to 0.5 ABs/cm2 or extracts containing asbestos body or amphibole fiber concentrations of at least 1900 or 390,000/g dry lung, respectively, will confirm an asbestos-related mesothelioma.