A CCL24-dependent pathway augments eosinophilic airway inflammation in house dust mite-challenged Cd163(-/-) mice.

CD163 is a macrophage scavenger receptor with anti-inflammatory and pro-inflammatory functions. Here, we report that alveolar macrophages (AMΦs) from asthmatic subjects had reduced cell-surface expression of CD163, which suggested that CD163 might modulate the pathogenesis of asthma. Consistent with this, house dust mite (HDM)-challenged Cd163(-/-) mice displayed increases in airway eosinophils and mucous cell metaplasia (MCM). The increased airway eosinophils and MCM in HDM-challenged Cd163(-/-) mice were mediated by augmented CCL24 production and could be reversed by administration of a neutralizing anti-CCL24 antibody. A proteomic analysis identified the calcium-dependent binding of CD163 to Dermatophagoides pteronyssinus peptidase 1 (Der p1). Der p1-challenged Cd163(-/-) mice had the same phenotype as HDM-challenged Cd163(-/-) mice with increases in airway eosinophils, MCM and CCL24 production, while Der p1 induced CCL24 secretion by bone marrow-derived macrophages (BMMΦs) from Cd163(-/-) mice, but not BMMΦs from wild-type (WT) mice. Finally, airway eosinophils and bronchoalveolar lavage fluid CCL24 levels were increased in Der p1-challenged WT mice that received adoptively transferred AMΦ's from Cd163(-/-) mice. Thus, we have identified CD163 as a macrophage receptor that binds Der p1. Furthermore, we have shown that HDM-challenged Cd163(-/-) mice have increased eosinophilic airway inflammation and MCM that are mediated by a CCL24-dependent mechanism.

Isolation rearing significantly perturbs brain metabolism in the thalamus and hippocampus.

Psychosocial neglect during childhood severely impairs both behavioral and physical health. The isolation rearing model in rodents has been employed by our group and others to study this clinical problem at a basic level. We previously showed that immediate early gene (IEG) expression in the hippocampus and medial prefrontal cortex (mPFC) is decreased in isolation-reared (IR) compared to group-reared (GR) rats. In the current study, we sought to evaluate: (1) whether these changes in IEG expression would be detected by the measurement of brain glucose metabolism using positron emission tomography (PET) with fluorodeoxyglucose (FDG) and (2) whether PET FDG could illuminate other brain regions with different glucose metabolism in IR compared to GR rats. We found that there were significant differences in FDG uptake in the hippocampus that were consistent with our findings for IEG expression (decreased mean FDG uptake in IR rats). In contrast, in the mPFC, the FDG uptake between IR and GR rats did not differ. Finally, we found decreased mean FDG uptake in the thalamus of the IR rats, a region we had not previously examined. The results suggest that PET FDG has the potential to be utilized as a biomarker of molecular changes in the hippocampus. Further, the differences found in thalamic brain FDG uptake suggest that further investigation of this region at the molecular and cellular levels may provide an important insight into the neurobiological basis of the adverse clinical outcomes found in children exposed to psychosocial deprivation.

Polymorphisms in candidate asthma genes.

The triad of reversible airway obstruction, bronchial hyperresponsiveness, and airway inflammation characterizes asthma. The etiology of asthma is complex and involves the interaction of multiple genetic foci and a variety of environmental factors, such as protein allergens, chemical sensitizers, and viral or bacterial proteins. Candidate asthma genes have been identified that may be linked or associated with the asthmatic phenotype. Potential candidate asthma genes include cytokine genes, receptor genes, transcription factors, immune recognition genes, and genes regulating lipid mediator generation. Although polymorphisms within either the promoter or coding region of individual asthma candidate genes have been identified, the association between these genetic polymorphisms and the asthmatic phenotype remains incompletely defined. Furthermore, genetic polymorphisms mediating the asthmatic phenotype are rarely identified in individual patients. This manuscript reviews several of the specific mutations and polymorphisms that have been identified in candidate asthma genes, such as the high affinity IgE receptor, the beta2-adrenergic receptor, the interleukin-4 promoter and receptor, the tumor necrosis factor gene, and the 5-lipoxygenase promoter.

Pneumocystis carinii pneumonia in patients without HIV infection.

Pneumocystis carinii is an important, but sporadic, opportunistic pulmonary pathogen in immunosuppressed HIV seronegative persons. Historically, patients at highest risk for P. carinii pneumonia are included infants with severe malnutrition, children with primary immunodeficiencies, patients with hematological malignancies, and recipients of solid organ or bone marrow transplants. Recently, solid tumor patients, in particular those receiving high-dose corticosteroids for brain neoplasms, and patients with inflammatory or collagen-vascular disorders, especially patients with Wegener granulomatosis receiving immunosuppressive therapy, have been identified as subgroups at increased risk for P. carinii pneumonia. Other factors associated with P. carinii pneumonia include the intensity of the immunosuppressive regimen and tapering doses of corticosteroids. Because P. carinii pneumonia is associated with significant morbidity and mortality, it is important to identify high-risk patient populations to administer effective chemoprophylactic agents, such as trimethoprim-sulfamethoxazole.

Tumor necrosis factor-alpha stimulates human Clara cell secretory protein production by human airway epithelial cells.

Clara cell secretory protein (CCSP), or CC10, is an inhibitor of secretory phospholipase A2 which may be produced by phagocytic cells and by a variety of other cells in the airway. Tumor necrosis factor-alpha (TNF-alpha) is capable of activating phospholipases and inducing the expression of a variety of genes in the airway epithelium which may modulate the airway inflammatory response. Therefore, it was of interest to determine whether this proinflammatory cytokine could induce the production of a counterregulatory protein such as CCSP which might modulate the production of eicosanoid mediators in the airway. Using a human bronchial epithelial cell line (BEAS-2B), CCSP messenger RNA (mRNA) levels were detected by ribonuclease protection assay. TNF treatment of these cells increased CCSP mRNA levels in a time- and dose-dependent manner. The CCSP mRNA level increased in response to TNF-alpha (20 ng/ml) stimulation after 8 to 36 h with the peak increase at 18 h. Immunoblotting of CCSP protein released into the culture media demonstrated that TNF-alpha induced the synthesis and secretion of CCSP protein in a time-dependent manner over 8 to 18 h. The results of a CCSP reporter gene activity assay, nuclear run-on assay, and CCSP mRNA half-life assay indicated that the TNF-alpha-induced increases in CCSP gene expression are regulated at the post-transcriptional level. We conclude that TNF-alpha induces airway epithelial cell expression of human CCSP protein and may modulate airway inflammatory responses in this manner.

The major surface glycoprotein of Pneumocystis carinii induces release and gene expression of interleukin-8 and tumor necrosis factor alpha in monocytes.

Recent studies suggest that interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) may play a central role in host defense and pathogenesis during Pneumocystis carinii pneumonia. In order to investigate whether the major surface antigen (MSG) of human P. carinii is capable of eliciting the release of IL-8 and TNF-alpha, human monocytes were cultured in the presence of purified MSG. MSG-stimulated cells released significant amounts of IL-8 within 4 h, and at 20 h, cells stimulated with MSG released 45.5 +/- 9.3 ng of IL-8/ml versus 3.7 +/- 1.1 ng/ml for control cultures (P = 0.01). In a similar fashion, MSG elicited release of TNF-alpha. Initial increases were also seen at 4 h, and at 20 h, TNF-alpha levels reached 6.4 +/- 1.1 ng/ml, compared to 0.08 +/- 0.01 ng/ml for control cultures (P < 0.01). A concentration-dependent increase in IL-8 and TNF-alpha secretion was observed at 20 h with 0.2 to 5 microg of MSG/ml (P < 0.01). Secretion of IL-8 and TNF-alpha from MSG-stimulated monocytes at 20 h was inhibited by 60 and 86%, respectively, after coincubation with soluble yeast mannan (P = 0.01). With an RNase protection assay, increases in steady-state mRNA levels for IL-8 and TNF-alpha were detectable at 4 h. These data show that recognition of MSG by monocytes involves a mannose-mediated mechanism and results in the release of the proinflammatory cytokines IL-8 and TNF-alpha.

Antisense inhibition of 85-kDa cPLA2 blocks arachidonic acid release from airway epithelial cells.

Inflammatory cytokines play a critical role in the initiation and perpetuation of inflammation. Several cytokines are known to increase the production of arachidonic acid (AA) metabolites, which may mediate cytokine-induced acute and chronic inflammation. Although cytokines upregulate phospholipase A2 (PLA2) in several target cells, the contribution of individual PLA2 to cytokine-induced AA release and eicosanoid production remains unclear because of the existence of various forms of cellular PLA2. To examine the role of 85-kDa cytosolic PLA2 (cPLA2) in cytokine-induced AA release, a system was developed to inhibit the expression of cPLA2 in a human bronchial epithelial cell line (BEAS-2B cells) by antisense RNA. Cells stably expressing antisense cPLA2 exhibited decreased cPLA2 protein levels as well as decreased cPLA2 activity assayed in vitro. The effects of cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 alpha (IL-1 alpha) on the release of prelabeled [3H]AA were then tested in cells stably transfected with vector alone as well as cells transfected with cPLA2 antisense plasmid. IFN-gamma (300 U/ml), TNF-alpha (20 ng/ml), and IL-1 alpha (20 ng/ml) all induced a significantly increased release of prelabeled [3H]AA after 15 min to 2 h of treatment in control cells, and their effects were significantly reduced in cells transfected with cPLA2 antisense vector. These results demonstrate a critical role of cPLA2 in inflammatory cytokine-induced AA metabolism.

Acute respiratory failure in the HIV-seropositive patient.

Since approximately 40% to 65% of patients with AIDS will develop pulmonary disease, HIV-seropositive patients represent a large cohort of immunosuppressed individuals with the potential to progress to respiratory failure requiring mechanical ventilation and admission to the intensive care unit. This article reviews the cause, pathophysiology, diagnostic approach, and management of acute respiratory failure requiring mechanical ventilation in HIV-seropositive patients. Prognostic factors and survival rates for episodes of respiratory failure are also discussed. In addition, an overview of acute respiratory failure in pediatric AIDS patients is presented.

Extracellular release of the type I intracellular IL-1 receptor antagonist from human airway epithelial cells: differential effects of IL-4, IL-13, IFN-gamma, and corticosteroids.

Three IL-1R antagonists (IL-1Ra) exist: secreted IL-1Ra and intracellular IL-1Ra (icIL-1Ra) types I and II. We have previously reported that human airway epithelial cells (HAEC) express icIL-1Ra type I, which can be up-regulated by corticosteroids. This study assessed whether cytokines and corticosteroids differentially effect icIL-1Ra type I protein release from HAEC to the extracellular compartment. We report that icIL-1Ra type I mRNA and intracellular protein are up-regulated in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, in response to IL-4, IL-13, IFN-gamma, and dexamethasone. The icIL-1Ra type I protein was detected in concentrated cell culture supernatants from NCI-H292 cells and normal human bronchial epithelial cells. The release of biologically relevant concentrations of active IL-1Ra from normal human bronchial epithelial cells was demonstrated by the ability of a neutralizing anti-IL-1Ra Ab to augment IL-1beta-mediated IL-8 secretion. IL-4, IL-13, and IFN-gamma induced immunoreactive IL-1Ra release into supernatants from NCI-H292 cells. Dexamethasone inhibited constitutive and cytokine-induced release of immunoreactive IL-1Ra. The release of icIL-1Ra type I protein was not related to cytotoxicity, as measured by lactate dehydrogenase. We propose that icIL-1Ra type I release from HAEC represents a novel mechanism by which IL-1 bioactivity in the airway microenvironment may be modulated. Cytokine-mediated icIL-1Ra type I synthesis may increase both intracellular protein and release to the extracellular space, where cell surface IL-1R can be antagonized. In contrast, corticosteroid-induced increases in icIL-1Ra type I synthesis and inhibition of extracellular protein release promote accumulation of icIL-1Ra type I protein within the intracellular compartment.

Pneumocystis carinii.

Improved understanding of Pneumocystis carinii, in particular the widespread use of chemoprophylaxis, has resulted in a declining incidence of infection in patients infected with HIV since the late 1980s. Despite these advances, P. carinii pneumonia continues to represent an important cause of pulmonary disease in HIV-seropositive individuals who do not receive chemoprophylaxis or when breakthrough episodes occur. This article reviews the history, biology, clinical manifestations, prognostic markers, therapy, and chemoprophylaxis of P. carinii pneumonia in HIV-seropositive patients.

Corticosteroids induce intracellular interleukin-1 receptor antagonist type I expression by a human airway epithelial cell line.

Interleukin-1 (IL-1) is an important proinflammatory cytokine which may contribute to the pathogenesis of inflammatory airway disorders, such as asthma and cystic fibrosis. Interleukin-1 receptor antagonist (IL-1ra) is a naturally occurring IL-1 inhibitor which binds to IL-1 receptors without inducing agonist activity. Three IL-1ra isoforms have been identified: secreted IL-1ra (sIL-1ra), which is preferentially expressed by-inflammatory cells; intracellular IL-1ra (iIL-1ra) type I, which lacks a signal peptide and is preferentially expressed by epithelial cells; and iIL-1ra type II, which is identical to iIL-1ra type I except for the insertion of an additional 21 amino acids. The goal of this study was to assess whether airway epithelial cell iIL-1ra type I production can be regulated by corticosteroids. First, using reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting, we confirm that normal human bronchial epithelial (NHBE) cells and a human pulmonary mucoepidermoid carcinoma cell line (NCI-H292) express intracellular IL-1ra type I messenger RNA (mRNA) and protein. Second, using immunoblotting and ELISA, we report that dexamethasone induces time- and concentration-dependent increases in iIL-1ra type I protein within NCI-H292 cell lysates. Lastly, utilizing a ribonuclease protection assay, we report that dexamethasone induces concentration-dependent increases in iIL-1ra type I mRNA levels in NCI-H292 cells. These data suggest that corticosteroid-mediated induction of iIL-1ra type I mRNA and protein by human bronchial epithelial cells represents a novel mechanism by which IL-1-mediated airway inflammatory events might be regulated.

Protein kinase C, interleukin-1 beta, and corticosteroids regulate shedding of the type I, 55 kDa TNF receptor from human airway epithelial cells.

Tumor necrosis factor (TNF) may contribute to the pathogenesis of inflammatory airway disorders via the regulation of inflammatory and cellular immune responses. Shed cell surface TNF receptors can act as soluble TNF binding proteins and modulate TNF biological activity. We report that normal human airway epithelial cells, as well as two human airway epithelial cell lines, shed soluble type I TNF receptors (sTNF-RI) in a concentration-dependent fashion following protein kinase C (PKC) activation by PMA. Interleukin (IL)-1beta also induced concentration-dependent sTNF-RI shedding from NCI-H292 cells, which could be inhibited by the PKC inhibitor calphostin C. Since corticosteroids are commonly utilized as antiinflammatory agents in airway disorders, the effect of dexamethasone on sTNF-RI release was assessed. Dexamethasone inhibited constitutive, as well as PMA- and IL-1beta-mediated sTNF-RI release from NCI-H292 cells in a concentration-dependent fashion. Furthermore, dexamethasone increased while PMA decreased total cellular 55 kDa TNF-RI protein as detected by immunoblotting. These changes in total cellular 55kDa TNF-RI protein did not appear to be mediated at the mRNA level, as assessed by ribonuclease protection assays. This suggests that sTNF-RI shedding represents a mechanism by which airway epithelial cells can actively participate in local cytokine networks and modulate TNF-mediated inflammation. Furthermore, since corticosteroids inhibit sTNF-RI release and are known to downregulate TNF synthesis, this may represent a mechanism by which equilibrium between TNF ligand and soluble binding protein is maintained in the airway microenvironment.

NIH conference. Airway inflammation.

Diseases characterized by airway inflammation, excessive airway secretion, and airway obstruction affect a substantial proportion of the population. These diseases include asthma, chronic bronchitis, bronchiectasis, and cystic fibrosis. Asthma and chronic bronchitis may affect 25 million persons in the United States. Much progress has been made in the last decade toward an understanding of the mechanisms underlying chronic airway inflammation; recent work has resulted in several new concepts of the initiation and maintenance of airway inflammation. Airway production of chemokines, cytokines, and growth factors in response to irritants, infectious agents, and inflammatory mediators may play an important role in the modulation of acute and chronic airway inflammation. Lipid mediators may be produced by resident airway cells and by inflammatory cells; production of these mediators may also be altered by inflammatory cytokines. Increased airway obstruction may be related to intercurrent viral respiratory infection and to the induction of airway inflammation and airway hyperreactivity that results from such infection. Furthermore, several models exist to explain the processes by which airway inflammation is perpetuated in diseases such as asthma and chronic bronchitis. These include neurogenic inflammation, the perpetuation of the acute inflammatory response, and cycles of airway epithelial cell-mediated and inflammatory cell-mediated recruitment and activation of inflammatory cells. An understanding of these mechanisms of airway inflammation may provide the clinician with new therapeutic approaches to the treatment of these common and chronic diseases.

Bronchial epithelial cell-cytokine interactions in airway inflammation.

A variety of cytokine bronchial cell interactions may play an important role in normal host defense as well as in the pathogenesis of inflammatory airway disorders such as asthma, cystic fibrosis, acute and chronic bronchitis, and bronchiectasis. First, airway epithelial cells may participate in local cytokine networks by synthesizing interleukins, chemokines, colony stimulating factors and growth factors in response to inflammatory mediators. Bronchial epithelial cell derived cytokines may thereby amplify ongoing inflammatory processes via the recruitment and activation of specific subsets of inflammatory cells, as well as by prolonging their survival in the airway microenvironment. Second, airway epithelial cells can initiate inflammatory cascades by generating cytokines in direct response to viral and bacterial products, noxious gases, and sensitizing chemicals. Third, airway epithelial cells represent targets for paracrine acting cytokines, which may then modulate bronchial epithelial cell functions. Finally, airway epithelial cells may modulate ongoing inflammatory events in the airway microenvironment via the shedding of soluble TNF receptors. Cytokine-bronchial epithelial cell interactions represent an important mechanism by which inflammatory events in the airway microenvironment can be regulated and represent potential targets for novel anti-inflammatory therapies in airway disorders.

Tumor necrosis factor-alpha induces mucin hypersecretion and MUC-2 gene expression by human airway epithelial cells.

Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional, proinflammatory cytokine that is capable of activating a diverse number of target genes within multiple cell types. Little information is known regarding the role of TNF-alpha in the regulation of human airway mucin hypersecretion and MUC-2 gene expression. To assess the effect of TNF-alpha exposure on mucin secretion, human airway organ cultures and primary cultures of human airway epithelial cells were stimulated with 20 ng/ml of recombinant human TNF-alpha and mucin secretion quantitated by an enzyme-linked immunosorbent assay using a specific monoclonal antibody directed against human airway mucin. Significant increases in mucin secretion from human airway organ cultures were initially detected at 1 h, peaked at 8 h, and persisted for 24 h. The TNF-alpha-mediated mucin hypersecretion at 8 h was concentration dependent. Significant increases in mucin secretion from primary cultures of human airway epithelial cells were initially detected at 4 h, peaked at 48 h, and persisted for 72 h after stimulation with 20 ng/ml of recombinant human TNF-alpha. The TNF-alpha-mediated mucin hypersecretion at 48 h from primary cultures of human airway epithelial cells was inhibited by coincubation with soluble 55 kD, type I TNF receptors. Using reverse transcription-polymerase chain reaction and a human pulmonary mucoepidermoid carcinoma cell line (NCI-H292), increases in MUC-2 steady-state mRNA levels were first detectable after 30 min of TNF-alpha stimulation and persisted for 24 h. Cycloheximide did not inhibit TNF-alpha-mediated MUC-2 mRNA expression at 1 h, suggesting that new protein translation was not required.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet-activating factor induces airway mucin release via activation of protein kinase C: evidence for translocation of protein kinase C to membranes.

Platelet-activating factor (PAF), a proinflammatory lipid mediator, is a potent airway mucin secretagogue. This study assessed the role of protein kinase C (PKC) in PAF-induced mucin release from primary cultures of feline tracheal epithelial cells (FTEC). Mucin secretion was quantitated by enzyme-linked immunosorbent assay using a monoclonal antibody raised against airway mucin-type glycoproteins. Coincubation of FTEC with PAF (5 microM) and pharmacologic PKC inhibitors, sphingosine, H7, or calphostin C, inhibited PAF-induced mucin secretion at 30 min. The PKC inhibitors produced a concentration-dependent, noncytotoxic inhibition. Exposure of FTEC with the PKC activator phorbol 12-myristate 13-acetate (PMA), failed to increase the release of mucin. Stimulation of FTEC with PAF caused a transient increase of membrane-bound PKC activity after 5 min of stimulation. PMA also induced the translocation of PKC activity from the cytosol to the membrane fraction, which was still present after 15 min of exposure. Determination of the specific PKC isozyme(s) involved in PAF-induced mucin release was performed by immunoblot analysis of the subcellular fractions using a battery of antibodies against various PKC isozymes (anti-PKC alpha, beta, delta, gamma, epsilon, and zeta). We found that PKC zeta (mol wt approximately 70 kD) was a major identifiable PKC isozyme present in the cytosolic fraction of FTEC. Furthermore, PKC zeta isozyme was also found to translocate to the membrane fraction following PAF exposure. Thus, these results demonstrate the crucial role of PKC in the intracellular events that culminate in mucin release following PAF stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Interferon-gamma induces the synthesis and activation of cytosolic phospholipase A2.

Both IFN-alpha/beta and IFN-gamma have recently been demonstrated to induce a rapid but transient activation of phospholipase A2 (PLA2) in BALB/c 3T3 fibroblasts and a human neuroblastoma cell line. We report that IFN-gamma induces the synthesis and prolonged activation of cytosolic phospholipase A2 (cPLA2) in a human bronchial epithelial cell line (BEAS 2B). Treatment of the cells with IFN-gamma (300 U/ml) increased the release of [3H]arachidonic acid (AA) from prelabeled cells with a maximal effect at 12 h after stimulation. The increased [3H]AA release was inhibited by the PLA2 inhibitor p-bromophenacyl bromide (10(-5) M). Calcium ionophore A23187 (10(-5) M) further increased the [3H]AA release from the IFN-gamma-treated cells. Subcellular enzyme activity assay revealed that IFN-gamma increased PLA2 activity in both the cytosol and membrane fractions with a translocation of the cPLA2 to cell membranes in a Ca(2+)-free cell lysing buffer. Treatment with IFN-gamma also induced the release of 15-HETE, an arachidonic acid metabolite. Immunoblot showed that IFN-gamma induced the synthesis of cPLA2 protein. Nuclear run-on assay demonstrated that IFN-gamma initiated cPLA2 gene transcription within 15 min, and this effect was sustained at 4 h and returned to near control level at 12 h. The cPLA2 mRNA level was assayed by reverse transcription and PCR. IFN-gamma was found to increase the cPLA2 mRNA after 2-24 h treatment. Furthermore, the IFN-gamma induced cPLA2 mRNA increase was blocked by inhibitors of protein kinase C and calcium/calmodulin-dependent protein kinases, suggesting the involvement of these protein kinases in IFN-gamma-induced gene expression of cPLA2. This study shows that IFN-gamma induces the synthesis and prolonged activation of cPLA2.

Corticosteroids differentially regulate secretion of IL-6, IL-8, and G-CSF by a human bronchial epithelial cell line.

Human airway epithelial cells play an active role in modulating airway inflammation by elaborating a variety of proinflammatory molecules, including cytokines. The purpose of this study was to define the role of corticosteroids in the regulation of cytokine gene transcription and secretion by human bronchial epithelial cells. In particular, we assessed whether dexamethasone was capable of inhibiting the tumor necrosis factor-alpha (TNF-alpha)-mediated secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), and granulocyte colony-stimulating factor (G-CSF) by a human bronchial epithelial cell line (BEAS-2B). Stimulation with 20 ng/ml of TNF-alpha resulted in significant increases in secretion of immunoreactive IL-6, IL-8, and G-CSF that were maximal at 24 h. TNF-alpha-mediated IL-6, IL-8, and G-CSF secretion was concentration dependent and specific. In addition, stimulation with TNF-alpha resulted in significant increases in the quantity of IL-6, IL-8, and G-CSF mRNA as detected by reverse-transcription polymerase chain reaction. Dexamethasone preconditioning significantly inhibited both the secretion of immunoreactive IL-6 and the accumulation of IL-6 mRNA. Although dexamethasone appeared to reduce both the secretion of immunoreactive IL-8 and accumulation of IL-8 mRNA, the inhibitory effects did not reach statistical significance. Finally, dexamethasone did not inhibit either the secretion of immunoreactive G-CSF or the accumulation of G-CSF mRNA. In summary, our results suggest that corticosteroids have a differential effect on the regulation of cytokine secretion by human bronchial epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Approach to the immunocompromised host with pulmonary symptoms.

Respiratory disease is common in patients who are immunocompromised, which may be because of opportunistic infection, non-infectious processes related to the underlying disease, or therapy instituted for treatment. Approaching pulmonary symptoms in an immunocompromised host is a complex challenge because the symptoms represent a diverse spectrum of disease. In addition to the routine clinical evaluation, this article reviews four diagnostic procedures to characterize pulmonary disease. Current concepts regarding the prevention of infection are also addressed.