Histological Diagnoses of Military Personnel Undergoing Lung Biopsy After Deployment to Southwest Asia.

INTRODUCTION: The current understanding of associations between lung disease and military deployment to Southwest Asia, including Iraq and Afghanistan, is both controversial and limited. We sought to clarify the relation between military deployment and biopsy-proven lung disease. METHODS: Retrospective data were analyzed for military personnel with non-neoplastic lung biopsies evaluated at the Armed Forces Institute of Pathology or Joint Pathology Center (January 2005 to December 2012). RESULTS: Of 391 subjects, 137 (35.0%) had deployed to Southwest Asia prior to biopsy. Compared to non-deployed subjects, those deployed were younger (median age 37 vs. 51 years) with higher representation of African Americans (30.0 vs. 16.9%). Deployed patients were more likely diagnosed with non-necrotizing granulomas (OR 2.4). Non-deployed subjects had higher frequency of idiopathic interstitial pneumonias, particularly organizing pneumonia. Prevalence of small airways diseases including constrictive bronchiolitis was low. CONCLUSIONS: This study provides a broader understanding of diversity of biopsy-proven non-neoplastic lung disease as it relates to military deployment to Southwest Asia and importantly did not show an increased prevalence of small airway disease to include constrictive bronchiolitis.

Endothelial GATA-6 deficiency promotes pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by pulmonary vasculopathy with elevation of pulmonary artery pressure, often culminating in right ventricular failure. GATA-6, a member of the GATA family of zinc-finger transcription factors, is highly expressed in quiescent vasculature and is frequently lost during vascular injury. We hypothesized that endothelial GATA-6 may play a critical role in the molecular mechanisms underlying endothelial cell (EC) dysfunction in PAH. Here we report that GATA-6 is markedly reduced in pulmonary ECs lining both occluded and nonoccluded vessels in patients with idiopathic and systemic sclerosis-associated PAH. GATA-6 transcripts are also rapidly decreased in rodent PAH models. Endothelial GATA-6 is a direct transcriptional regulator of genes controlling vascular tone [endothelin-1, endothelin-1 receptor type A, and endothelial nitric oxide synthase (eNOS)], pro-inflammatory genes, CX3CL1 (fractalkine), 5-lipoxygenease-activating protein, and markers of vascular remodeling, including PAI-1 and RhoB. Mice with the genetic deletion of GATA-6 in ECs (Gata6-KO) spontaneously develop elevated pulmonary artery pressure and increased vessel muscularization, and these features are further exacerbated in response to hypoxia. Furthermore, innate immune cells including macrophages (CD11b(+)/F4/80(+)), granulocytes (Ly6G(+)/CD45(+)), and dendritic cells (CD11b(+)/CD11c(+)) are significantly increased in normoxic Gata6-KO mice. Together, our findings suggest a critical role of endothelial GATA-6 deficiency in development and disease progression in PAH.

Small-for-Size Liver Transplantation Increases Pulmonary Injury in Rats: Prevention by NIM811.

Pulmonary complications after liver transplantation (LT) often cause mortality. This study investigated whether small-for-size LT increases acute pulmonary injury and whether NIM811 which improves small-for-size liver graft survival attenuates LT-associated lung injury. Rat livers were reduced to 50% of original size, stored in UW-solution with and without NIM811 (5 µM) for 6 h, and implanted into recipients of the same or about twice the donor weight, resulting in half-size (HSG) and quarter-size grafts (QSG), respectively. Liver injury increased and regeneration was suppressed after QSG transplantation as expected. NIM811 blunted these alterations >75%. Pulmonary histological alterations were minimal at 5-18 h after LT. At 38 h, neutrophils and monocytes/macrophage infiltration, alveolar space exudation, alveolar septal thickening, oxidative/nitrosative protein adduct formation, and alveolar epithelial cell/capillary endothelial apoptosis became overt in the lungs of QSG recipients, but these alterations were mild in full-size and HSG recipients. Liver pretreatment with NIM811 markedly decreased pulmonary injury in QSG recipients. Hepatic TNFα and IL-1ß mRNAs and pulmonary ICAM-1 expression were markedly higher after QSG transplantation, which were all decreased by NIM811. Together, dysfunctional small-for-size grafts produce toxic cytokines, leading to lung inflammation and injury. NIM811 decreased toxic cytokine formation, thus attenuating pulmonary injury after small-for-size LT.

Indium lung disease.

BACKGROUND: Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. METHODS: To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. RESULTS: Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. CONCLUSIONS: Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies.

Leukocyte-mediated cell dissemination and metastasis: findings from multiple types of human tumors.

Our previous studies revealed that leukocyte infiltration could trigger human breast and prostate tumor invasion through focal disruptions of the tumor capsule, which selectively favors monoclonal proliferation of tumor progenitors or a biologically more aggressive cell clone overlying the focal disruptions. Our current study, involving multiple types of human tumors, further shows that leukocyte infiltration could also trigger tumor metastasis through the following pathways: [1] more leukocytes migrate to focally disrupted tumor capsules, which forms leukocyte aggregates surrounding newly formed tumor cell clusters, [2] the physical movement of leukocytes into proliferating tumor cells disrupts the intercellular junctions and cell-surface adhesion molecules, causing the disassociation of tumor cells from the tumor core, [3] leukocytes are conjoined with some of these tumor cells through plasma membrane fusion, creating tumor cell-leukocyte chimeras (TLCs), and [4] the leukocyte of TLCs impart migratory capacity to associated tumor cell partners, physically dragging them to different tissue sites. Our findings suggest a novel pathway for tumor cell dissemination from the primary sites and the subsequent journey to new sites. Our findings also provide a unique explanation for the cellular mechanism of leukocytes on tumor invasion and metastasis. If confirmed, our hypothesis and technical approach may significantly facilitate early detection and intervention of tumor invasion and metastasis.

Comparison of cardiovascular risk factors for high brachial pulse pressure in blacks versus whites (Charleston Heart Study, Evans County Study, NHANES I and II Studies).

We examined whether the risk factors for increased brachial pulse pressure (PP) are similar for blacks and whites. Many studies have reported the strong association of increased brachial PP and the prevalence of cardiovascular disease. Participants were from 4 major epidemiologic studies in the United States (26,083 subjects): Charleston Heart Study, Evans County Heart Study, the National Health and Nutrition Examination Survey (NHANES) I study, and the NHANES II study. At baseline, there was no history or clinical evidence of coronary heart disease (CHD). The CHD mortality as a function of brachial PP and the association of traditional risk factors for CHD with PP were analyzed for each of the 4 studies and for the 4 studies combined. Multiple regression analysis showed that the most significant predictors of high brachial PP are body mass index > or =30 kg/m(2) (regression coefficient 3.79, p <0.0001), diabetes mellitus (5.14, p <0.0001), serum total cholesterol > or =240 mg/dl (0.51, p <0.0157), age (0.60, p <0.0001), gender (-1.77, p <0.0001), and race (3.75, p <0.0001). In conclusion, the same risk factors for CHD (namely, increase in body mass index > or =30 kg/m(2), diabetes mellitus, hypercholesterolemia, and age) are significantly associated with high brachial PP for blacks and whites. These risk factors were stronger in whites compared with blacks. However, female gender and age variables were even more associated with brachial PP in blacks. Smoking was significant but not reflected in peripheral brachial PP as it is in aortic PP.

Antifibrotic properties of caveolin-1 scaffolding domain in vitro and in vivo.

Lung fibrosis involves the overexpression of ECM proteins, primarily collagen, by alpha-smooth muscle actin (ASMA)-positive cells. Caveolin-1 is a master regulator of collagen expression by cultured lung fibroblasts and of lung fibrosis in vivo. A peptide equivalent to the caveolin-1 scaffolding domain (CSD peptide) inhibits collagen and tenascin-C expression by normal lung fibroblasts (NLF) and fibroblasts from the fibrotic lungs of scleroderma patients (SLF). CSD peptide inhibits ASMA expression in SLF but not NLF. Similar inhibition of collagen, tenascin-C, and ASMA expression was also observed when caveolin-1 expression was upregulated using adenovirus. These observations suggest that the low caveolin-1 levels in SLF cause their overexpression of collagen, tenascin-C, and ASMA. In mechanistic studies, MEK, ERK, JNK, and Akt were hyperactivated in SLF, and CSD peptide inhibited their activation and altered their subcellular localization. These studies and experiments using kinase inhibitors suggest many differences between NLF and SLF in signaling cascades. To validate these data, we determined that the alterations in signaling molecule activation observed in SLF also occur in fibrotic lung tissue from scleroderma patients and in mice with bleomycin-induced lung fibrosis. Finally, we demonstrated that systemic administration of CSD peptide to bleomycin-treated mice blocks epithelial cell apoptosis, inflammatory cell infiltration, and changes in tissue morphology as well as signaling molecule activation and collagen, tenascin-C, and ASMA expression associated with lung fibrosis. CSD peptide may be a prototype for novel treatments for human lung fibrosis that act, in part, by inhibiting the expression of ASMA and ECM proteins.

Fatal neurotoxic response to neuroleptic medications: case report and review of the literature.

Neuroleptic malignant syndrome (NMS) is a diagnosis of exclusion difficult to make due to a lack of pathognomonic features. Diagnosing NMS by postmortem examination becomes increasingly challenging when possible underlying brain pathology is obscured. The diagnosis is based on clinical history and laboratory findings. Autopsy and histologic findings, if any, usually are reflective of hyperthermia or complications (eg, aspiration pneumonia) of NMS. The authors describe a case of a 36-year-old Hispanic woman with a presumptive diagnosis of pseudoseizures, treated with various combinations of neuroleptic medications over a 6-week period prior to her sudden, unexpected, in-hospital death. Neuroleptic malignant syndrome is likely to have contributed to this patient's death. Confounding factors and medicolegal issues of a postmortem diagnosis of NMS are discussed.

Verapamil toxicity: an unusual case report and review of the literature.

Verapamil blocks the rapid influx of calcium into the cardiac myocytes of the cardiac conduction system and smooth muscle of the vasculature, resulting in decreased myocardial contractility, prolonged conduction time, and vascular relaxation. A sustained-release form, verapamil SR (or ER), is available that contains higher levels of medication and requires only once-daily dosing. The majority of reported fatal cases of verapamil toxicity are due to massive, intentional overdoses. Herein, we present an unusual case of fatal verapamil SR toxicity in a 57-year-old female that resulted from accidental overdose of only 3 tablets (720 mg), as witnessed by the decedent's daughter. In spite of the low dose ingested, the postmortem cardiac blood verapamil level was clearly toxic (6000 ng/mL, or 6 mg/L). Her preexisting medical conditions included hypercholesterolemia, hypertension, iron deficiency anemia, diabetes mellitus, and associated mild chronic renal failure. Complicating factors, which likely include the decedent's preexisting renal and cardiac disease, and a review of the available literature will be discussed.

Iatrogenic deaths following treatment for hypertrophic obstructive cardiomyopathy: case reports and an approach to the autopsy and death certification.

Hypertrophic cardiomyopathy (HCM) is a disease process which results in a large, heavy heart, with hypertrophy of the interventricular septum (IVS) and left ventricle. HCM accounts for a significant number of cases of sudden cardiac death each year, most infamously in young athletes. The prevalence of the disease has increased over the past several years due to advances in clinical diagnosis and molecular genetic studies. Over this same period, new forms of treatment also have emerged. One such treatment is alcohol septal ablation (ASA). ASA is a procedure performed by a cardiologist, via cardiac catheterization, by injecting pure ethanol into selected arteries which supply the IVS, resulting in a targeted myocardial infarction. This infarct then retracts and forms a scar, decreasing the outflow obstruction and improving the patient's clinical symptoms.The authors report 2 cases of death following ASA treatment of HCM. The first, a 56-year-old male, had his ASA procedure 10 days prior to death. The second decedent, a 76-year-old female, had her procedure only 30 hours before death. These case reports are followed by a discussion about HCM, including pathology, treatments, and treatment-related pathology, before closing with a discussion about death certification in the cases presented and therapy-related deaths in general.

Immunohistochemical distribution of sphingosine kinase 1 in normal and tumor lung tissue.

Sphingosine kinase 1 (SK1) is a key enzyme critical to the sphingolipid metabolic pathway responsible for catalyzing the formation of the bioactive lipid sphingosine-1-phosphate. SK1-mediated production of sphingosine-1-phosphate has been shown to stimulate such biological processes as cell growth, differentiation, migration, angiogenesis, and inhibition of apoptosis. In this study, cell type-specific immunolocalization of SK1 was examined in the bronchus/terminal bronchiole of the lung. Strong immunopositive staining was evident at the apical surface of pseudostratified epithelial cells of the bronchus and underlying smooth muscle cells, submucosal serous glands, immature chondrocytes, type II alveolar cells, foamy macrophages, endothelial cells of blood vessels, and neural bundles. Immunohistochemical screening for SK1 expression was performed in 25 samples of normal/tumor patient matched non-small-cell lung cancer tissue and found that 25 of 25 tumor samples (carcinoid [5 samples], squamous [10 samples], and adenocarcinoma tumors [10 samples]), exhibited overwhelmingly positive immunostaining for SK1 as compared with patient-matched normal tissue. In addition, an approximately 2-fold elevation of SK1 mRNA expression was observed in lung cancer tissue versus normal tissue, as well as in several other solid tumors. Taken together, these findings define the localization of SK1 in lung and provide clues as to how SK1 may play a role in normal lung physiology and the pathophysiology of lung cancer.

Mosaic duplication 1(q11q44) in an infant with nephroblastomatosis and mineralization of extraplacental membranes.

Partial trisomy of 1q is rare. Only 32 cases of isolated partial trisomy 1q have been previously reported. From these cases, a characteristic phenotype is beginning to emerge. We present a case of mosaic duplication of 1q [46,XX,dup (1)(q11q44)/46,XX]. Many features of our patient have been described in previous patients, thus supporting the emerging phenotype. Two particular features, however, have not been previously described. The present case demonstrated extensive mineralization of the extraplacental membranes and bilateral nephromegaly, with an extreme form of diffusely hyperplastic perilobar nephroblastomatosis. Clinical comparison is made between our case and previously reported cases, and the clinical significance of the unique findings are reviewed and discussed.

Ancillary studies in amniotic fluid embolism: a case report and review of the literature.

The incidence of amniotic fluid embolism during pregnancy is approximately 1/50,000 and has a mortality rate in excess of 80%. The postmortem diagnosis of amniotic fluid embolism can be challenging for forensic investigators and pathologists. At autopsy, usually signs of disseminated intravascular coagulation suggest an amniotic fluid embolism. A definitive diagnosis of amniotic fluid embolism cannot be made until ancillary studies are performed on the decedent's tissues. We report a case of a 37-year-old G3P2 white female who was 36 weeks gestation when her membranes spontaneously ruptured. She suddenly became breathless, went into cardiogenic shock, and died. The autopsy revealed gross and microscopic findings of amniotic fluid embolism, which was confirmed with ancillary studies consisting of special stains, immunohistochemistry, and a serum tryptase level. The authors hope this case report, including gross and microscopic autopsy findings with procedural and ancillary studies, and review of the literature will help investigators and pathologists in the diagnosis of amniotic fluid embolism.

Distinct PKC isoforms mediate cell survival and DNA synthesis in thrombin-induced myofibroblasts.

Thrombin activates protease-activated receptor (PAR)-1 and induces a myofibroblast phenotype in normal lung fibroblasts that resembles the phenotype of scleroderma lung fibroblasts. We now demonstrate that PAR-1 expression is dramatically increased in lung tissue from scleroderma patients, where it is associated with inflammatory and fibroproliferative foci. We also observe that thrombin induces resistance to apoptosis in normal lung fibroblasts, and this process is regulated by protein kinase C (PKC)-epsilon but not by PKC-alpha. Overexpression of a constitutively active (c-a) form of PAR-1 or PKC-epsilon significantly inhibits Fas ligand-induced apoptosis in lung fibroblasts, whereas scleroderma lung fibroblasts are resistant to apoptosis de novo. Thrombin translocates p21Cip1/WAF1, a signaling molecule downstream of PKC, from the nucleus to cytoplasm in normal lung fibroblasts mimicking the localization of p21Cip1/WAF1 in scleroderma lung fibroblasts. Overexpression of c-a PKC-alpha or PKC-epsilon results in accumulation of p21Cip1/WAF1 in the cytoplasm. Depletion of PKC-alpha or inhibition of mitogen-activated protein kinase (MAPK) blocks thrombin-induced DNA synthesis in lung fibroblasts. Inhibition of PKC by calphostin or PKC-alpha, but not PKC-epsilon, by antisense oligonucleotides prevents thrombin-induced MAPK phosphorylation and accumulation of G(1) phase regulatory protein cyclin D1, suggesting that PKC-alpha, MAPK, and cyclin D1 mediate lung fibroblast proliferation. These data demonstrate that two distinct PKC isoforms mediate thrombin-induced resistance to apoptosis and proliferation and suggest that p21Cip1/WAF1 promotes both phenomena.

Respiratory reovirus 1/L induction of intraluminal fibrosis, a model of bronchiolitis obliterans organizing pneumonia, is dependent on T lymphocytes.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinical syndrome characterized by perivascular/peribronchiolar leukocyte infiltration leading to the development of intraalveolar fibrosis. We have developed an animal model of BOOP where CBA/J mice infected with 1 x 10(6) plaque-forming units (PFU) reovirus 1/L develop follicular bronchiolitis and intraalveolar fibrosis similar to human BOOP. In this report, we demonstrate a role for T cells in the development of intraluminal fibrosis associated with BOOP. Corticosteroid treatment of reovirus 1/L-infected mice both inhibited the development of fibrotic lesions when administered early in the time-course and promoted the resolution of fibrotic lesions when corticosteroid administration was delayed. Further, the depletion of either CD4(+) or CD8(+) T cells before reovirus 1/L infection also inhibited fibrotic lesion development. Both corticosteroid treatment and depletion of CD4(+) or CD8(+) T cells also resulted in decreased expression of the proinflammatory and profibrotic cytokines, interferon (IFN)-gamma and monocyte chemoattractant protein-1 (MCP-1). Further, treatment of mice with a neutralizing monoclonal antibody to IFN-gamma also significantly inhibited the development of fibrosis. Taken together, these results suggest a significant role for T cells in the development of reovirus 1/L-induced BOOP fibrotic lesions in CBA/J mice and suggests that T(H)1-derived cytokines, especially IFN-gamma, may play a key role in fibrotic lesion development.

Contractile activity and smooth muscle alpha-actin organization in thrombin-induced human lung myofibroblasts.

Activated fibroblasts, or myofibroblasts, are crucial players in tissue remodeling, wound healing, and various fibrotic disorders, including interstitial lung fibrosis associated with scleroderma. Here we characterize the signaling pathways in normal lung fibroblasts exposed to thrombin as they acquire two of the main features of myofibroblasts: smooth muscle (SM) alpha-actin organization and collagen gel contraction. Our results show that the small G protein Rho is involved in lung myofibroblast differentiation. Thrombin induces Rho-35S-labeled guanosine 5'-O-(3-thiotriphosphate) binding in a dose-dependent manner. It potently stimulates Rho activity in vivo and initiates protein kinase C (PKC)-epsilon-Rho complex formation. Toxin B, which inactivates Rho by ADP ribosylation, inhibits thrombin-induced SM alpha-actin organization, collagen gel contraction, and PKC-epsilon-SM alpha-actin and PKC-epsilon-RhoA coimmunoprecipitation. However, it has no effect on PKC-epsilon activation or translocation of PKC-epsilon to the membrane. Overexpression of constitutively active PKC-epsilon and constitutively active RhoA induces collagen gel contraction or SM alpha-actin organization, whereas, individually, they do not perform these functions. We therefore conclude that the contractile activity of myofibroblasts induced by thrombin is mediated via PKC-epsilon- and RhoA-dependent pathways and that activation of both of these molecules is required. We postulate that PKC-epsilon-RhoA complex formation is an early event in thrombin activation of lung fibroblasts, followed by PKC-epsilon-SM alpha-actin coimmunoprecipitation, which leads to the PKC-epsilon-RhoA-SM alpha-actin ternary complex formation.

Differential role for T cells in the development of fibrotic lesions associated with reovirus 1/L-induced bronchiolitis obliterans organizing pneumonia versus Acute Respiratory Distress Syndrome.

Bronchiolitis obliterans organizing pneumonia (BOOP) and Acute Respiratory Distress Syndrome (ARDS) are two pulmonary diseases with fibrotic components. BOOP is characterized by perivascular/peribronchiolar leukocyte infiltration leading to the development of intra-alveolar fibrosis. ARDS is a biphasic disease that includes an acute phase, consisting of severe leukocyte infiltration, edema, hemorrhage, and the formation of hyaline membranes, and a chronic phase, which is characterized by persistent intra-alveolar and interstitial fibrosis. CBA/J mice infected with 1 x 10(6) plaque-forming units (pfu) reovirus 1/L develop follicular bronchiolitis and intra-alveolar fibrosis similar to BOOP. In contrast, CBA/J mice infected with 1 x 10(7) pfu reovirus 1/L develop histologic characteristics of ARDS including diffuse alveolar damage, hyaline membranes, and intra-alveolar fibrosis. In this report, we demonstrate a differential role for T lymphocytes in the development of fibrosis associated with BOOP versus ARDS. Neonatally thymectomized CBA/J mice infected with 1 x 10(7) pfu (ARDS) reovirus 1/L still develop the hallmark characteristics of ARDS, including a severe viral pneumonia with cellular infiltrates comprised mainly of macrophages and neutrophils, hyaline membrane formation, and hemorrhage during the acute phase of the disease and persistent intra-alveolar fibrosis during the chronic phase of the disease. In contrast, neonatally thymectomized CBA/J mice infected with 1 x 10(6) pfu (BOOP) reovirus 1/L do not develop intra-alveolar fibrosis associated with BOOP. Therefore, while T cells are necessary for the development of intraluminal fibrosis associated with BOOP, they are not necessary for the development of intraluminal fibrosis associated with ARDS. Furthermore, we suggest that interferon-gamma plays a key role in the fibrotic process and that elevated levels of interferon-gamma are associated with a continuum from least to more severe fibrosis.

Respiratory reovirus 1/L induction of diffuse alveolar damage: pulmonary fibrosis is not modulated by corticosteroids in acute respiratory distress syndrome in mice.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage (DAD) secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or noninfectious insult. We have previously described a unique animal model in which CBA/J mice infected with reovirus 1/L develop ARDS. This model recapitulates the histopathological changes observed in human ARDS, which consist of the overlapping phases of exudation, including the formation of hyaline membranes, regeneration, and healing via repair with fibrosis. In this report, we show that the development of DAD in the acute phase of the disease and intraalveolar fibrosis in the late phase of the disease was not modulated by treatment with methylprednisolone (MPS). In the presence or absence of MPS, the majority of cells infiltrating the lungs after reovirus 1/L infection were polymorphonuclear leukocytes and macrophages. A number of key proinflammatory and anti-inflammatory cytokines/chemokines that are observed in the BAL fluid of ARDS patients were also found in the lungs of mice after reovirus 1/L infection and were not modulated by MPS. These include interferon-gamma, interleukin-10, and monocyte chemoattractant protein. The histopathology, cytokine/chemokine expression, and response to corticosteroids in reovirus 1/L-induced ARDS are similar to what is observed in human patients, making this a clinically relevant model.