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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large body of clinical experience on the adverse consequences of cytokine administration has accumulated since the last decade. Side-effects reported after the therapeutic use of cytokines has provided evidence that activation of the immune response may sometimes have deleterious consequences. Several effects appeared as a direct consequence of the immune activation induced by cytokines, e.g. flu-like reactions, vascular leak syndrome. Cytokine-induced exacerbation of underlying diseases or immune dysregulation were other complications of growing concern. Interferon-alpha (IFN-alpha) treatment has now been clearly linked with the exacerbation or the occurrence of several types of autoantibodies or autoimmune diseases (thyroiditis, systemic lupus erythematosus, hematologic disorders, insulin-dependent diabetes mellitus) or diseases involving altered cell-mediated immune functions (inflammatory dermatologic diseases, nephritis, pneumonitis, colitis). By contrast immunological side-effects of IFN-beta and IFN-gamma have been seldom reported. However, the extent of clinical experience with both of these cytokines is still very limited. Interleukin-2 (IL-2) has also been implicated in various conditions that may involve immunopathological processes (thyroid disorders, rheumatoid arthritis, dermatological diseases, interstitial nephritis). Growth factors have been more specifically linked with the development or the exacerbation of dermatological inflammatory diseases through neutrophils, monocytes/macrophages or eosinophils activation (e.g. cutaneous vasculitis and generalized cutaneous eruption, Sweet's syndrome, bullous eruption, psoriasis). Exacerbation of autoimmune thyroiditis was described with granulocyte-macrophage colony-stimulating factor (GM-CSF) only. The immunogenicity of cytokines is also of great relevance and the occurrence of antibodies binding IFN-alpha and IFN-beta, IL2 and GM-CSF have been reported. While the clinical significance of non-neutralizing antibodies is not clearly established, an absence of response or reversal of clinical efficacy has been described in patients developing neutralizing antibodies. Finally, several isolated reports have recently suggested that IFN-alpha treatment may be associated with several immunosuppressive effects while IL-2 is clinically associated with an increased incidence of infectious complications.
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PMID:Immune-mediated side-effects of cytokines in humans. 863 83

Pneumocystis carinii (PC) is a leading cause of pneumonia in immunocompromised patients. Previous work has shown that fibronectin (Fn) and Fn-binding integrins mediate PC attachment to lung cells in vitro. Gamma-interferon (gamma-IFN) is a major factor in host defence against PC infection. To determine the effect of gamma-IFN on PC attachment to lung cells, the alveolar epithelial cell line A549 was incubated with gamma-IFN (0-10(4) U mL(-1)) and attachment of 51Cr-labelled PC to the A549 cells was quantified. PC attachment was significantly decreased (P < 0.01) by addition of gamma-IFN with no evidence of injury to either the PC or A549 cells. Effects of gamma-IFN on PC attachment were observed after 24 h and reached a maximum after 48 h of incubation. To investigate the mechanism of this decrease, we examined integrin expression on gamma-IFN-treated A549 cells. A549 cell expression of the alpha5 and beta1 integrin subunits was decreased, whereas expression of the alpha(v) subunit was unchanged. Northern blot analysis showed a similar decrease in mRNA for the alpha5 and beta1 integrins. Therefore, gamma-IFN-mediated inhibition of PC infection may, in part, result from inhibition of PC attachment to alveolar epithelial cells caused by gamma-IFN-induced decreases in alveolar integrin expression.
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PMID:Gamma-interferon inhibits Pneumocystis carinii attachment to lung cells by decreasing expression of lung cell-surface integrins. 904 72

Microbiologically-inapparent chlamydial infection may contribute towards the immunopathogenesis of these diseases. Although morphologically and physiologically aberrant non-cultivable chlamydiae can be induced reversibly in cell culture, evidence for these forms in infections of animals and humans is indirect. A mouse model of salpingitis caused by the mouse pneumonitis biovar of Chlamydia trachomatis (MoPn) was used to determine the existence of non-cultivable organisms in vivo. Following intravaginal inoculation, mice yielded high chlamydial counts for 7-14 dyas, with a decline in culture-positivity by 21-28 days. A significant elevation of IFN gamma production in infected tissues was measured for 21 days and, from 28-70 days, all mice were culture-negative and developed characteristic hydrosalpinges. MoPn was detected by PCR in vaginal swabs of 80% and 69% respectively of culture-negative animals at 21 and 28 days. In a second study, 100%, 63% and 50% of culture-negative genital tissue homogenates were PCR-positive at 21, 28 and 42 days. Immunosuppression with either cyclophosphamide or hydrocortisone failed to regenerate cultivable chlamydiae. Tissues were disrupted by homogenization and inoculated intranasally to MF1 mice which are extremely susceptible to MoPn, but all culture-negative specimens were non-infectious. The significance of the PCR-positive culture-negative specimens requires further investigation, since these may represent a non-cultivable state in the deeper tissues of the mouse genital tract which may be beyond the reach of reactivating triggers.
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PMID:Does Chlamydia trachomatis MoPn enter a microbiologically-inapparent state during experimental infection of the mouse genital tract? 904 99

Detection of Pneumocystis carinii by the polymerase chain reaction (PCR), based on the thymidylate synthase (TS) gene of rat P. carinii, is a specific and sensitive method for the detection of the parasite in respiratory samples. However, the use of the method is limited by a laborious phenol-chloroform DNA extraction method and an expensive and time-consuming hybridization procedure. For routine clinical samples, DNA preparation can be simplified and hybridization substituted by a nested PCR technique. Such a modified PCR procedure, based on the TS gene of P. carinii, was evaluated on 190 induced sputum samples from 50 immunosuppressed patients, infected with human immunodeficiency virus (HIV), with and without symptoms of P. carinii pneumonia (PCP). The PCR assay, preceded by a rapid DNA preparation (Wizard DNA Clean-up), detected P. carinii-DNA in 13/15 sputa containing parasites as seen by microscopy using immunocytochemical (IFL) staining, and in 10 additional sputum samples lacking demonstrable parasites by microscopy. These samples are to be considered as 'true' positives, since all but 2 were from patients, who developed a PCP within 1 year. We conclude that the nested PCR assay is more sensitive than IFL for the detection of P. carinii in AIDS patients, prior to the debut of PCP symptoms.
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PMID:A rapid and simple nested PCR assay for the detection of Pneumocystis carinii in sputum samples. 906 63

This study was undertaken to determine if recombinant interferon-gamma (rIFN-gamma) given every other day as maintenance therapy could prolong the survival of patients with small cell lung cancer (SCLC) who achieved a complete or nearly-complete response to induction therapy. A secondary endpoint was to assess the toxicity of alternate day doses of this treatment. One hundred and seventy seven patients in complete or nearly-complete response following chemotherapy with or without thoracic radiotherapy were studied. Patients were randomised to receive either rIFN-gamma 4 million units (0.2 mg) subcutaneously every other day for 4 months or observation. One hundred and twenty of the 127 registered patients were eligible; 59 patients received IFN and 61 patients without maintenance therapy were followed. Alternate day IFN was reasonably well tolerated by the majority of patients, but in 12% substantial non-haematological toxicity (including flu-like syndrome) occurred. One of 3 patients with pneumonitis died after having received 3.6 mg IFN. The median survival time from the date of randomisation was 8.9 months for the IFN arm and 9.9 months for the observation arm. rIFN-gamma at the dose and schedule used in this study failed to prolong response duration and survival in SCLC patients in complete or nearly-complete response. The toxicity seen with every other day doses of IFN was less than that reported with daily dosing. The hypothesis that this agent may increase the deleterious effects of radiation on normal lung tissue was supported by the development of pneumonitis in 3 cases of whom 1 had a fatal outcome. The results do not warrant further studies with rIFN-gamma on maintaining response in SCLC.
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PMID:Role of recombinant interferon-gamma maintenance in responding patients with small cell lung cancer. A randomised phase III study of the EORTC Lung Cancer Cooperative Group. 989 43

We reported a case of primary macroglobulinemia with stomach and pulmonary invasion. The patient was 71 years-old who had cervical lymphadenopathy and abdominal pain. Biopsy material of cervical lymph node showed non-Hodgkin's lymphoma, and he was diagnosed primary macroglobulinemia by IgM immunological histo-chemical staining of materials of stomach biopsies. Combination chemotherapies were not effective for the reduction of IgM-lambda protein, and organ invasion seemed to be progressive, so we tried interferon-alpha (IFN-alpha) to control M component. Daily injection of 6 megaunits of IFN-alpha induced significant reduction of M component and pulmonary invasion. This favorable changes were observed for 1 year. However, his pulmonary invasion on X-ray films relapsed and he died of respiratory failure by reason of severe pneumonia. IFN-alpha is currently available for myeloproliferative disease, especially chronic myelogenous leukemia and multiple myeloma. This case report showed that IFN-alpha was also available for primary macroglobulinemia.
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PMID:[Interferon-alpha treatment for chemotherapy-resistant primary macroglobulinemia with stomach and lung invasion]. 975 16

Human parainfluenza virus type 3 (HPIV3) infection causes severe damage to the lung epithelium, leading to bronchiolitis, pneumonia, and croup in newborns and infants. Cellular immunity that plays a vital role in normal antiviral action appears to be involved, possibly because of inappropriate activation, in the infection-related damage to the lung epithelium. In this study, we investigated the expression of major histocompatibility complex (MHC) class I and II molecules on human lung epithelial (A549) and epithelium-like (HT1080) cells following HPIV3 infection. MHC class I was induced by HPIV3 in these cells at levels similar to those observed with natural inducers such as beta and gamma interferon (IFN-beta and -gamma). MHC class II was also efficiently induced by HPIV3 in these cells. UV-irradiated culture supernatants from infected cells were able to induce MHC class I but not MHC class II, suggesting involvement of released factors for the induction of MHC class I. Quantitation of IFN types I and II in the culture supernatant showed the presence of IFN-beta as the major cytokine, while IFN-gamma was undetectable. Anti-IFN-beta, however, blocked the HPIV3-mediated induction of MHC class I only partially, indicating that viral antigens, besides IFN-beta, are directly involved in the induction process. The induction of MHC class I and class II directed by the viral antigens was confirmed by using cells lacking STAT1, an essential intermediate of the IFN signaling pathways. HPIV3 induced both MHC class I and class II molecules in STAT1-null cells. Furthermore, MHC class II was also induced by HPIV3 in cells defective in class II transactivator, an important intermediate of the IFN-gamma-mediated MHC class II induction pathway. Together, these data indicate that the HPIV3 gene product(s) is directly involved in the induction of MHC class I and II molecules. The induction of MHC class I and II expression by HPIV3 suggests that it plays a role in the infection-related immunity and pathogenesis.
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PMID:Human parainfluenza virus type 3 up-regulates major histocompatibility complex class I and II expression on respiratory epithelial cells: involvement of a STAT1- and CIITA-independent pathway. 988 46

The acute stages of infection with swine influenza virus (SIV), porcine respiratory coronavirus (PRCV) and porcine reproductive-respiratory syndrome virus (PRRSV) were shown to differ in terms of clinical and lung inflammatory effects and proinflammatory cytokine profiles in bronchoalveolar lavage (BAL) fluids. Caesarian-derived colostrum-deprived pigs were inoculated intratracheally with one of the three viruses. SIV infection was followed within 1 day post inoculation (d PI) by characteristic respiratory and general signs, and excessive lung epithelial desquamation and neutrophil infiltration (38 to 56 per cent of BAL cells at 1 d PI vs 0 to 1 per cent in controls). High concentrations of bioactive interferon-alpha (IFN -alpha), tumour necrosis factor-alpha (TNF -alpha) and interleukin-1 (IL -1) coincided with peak symptoms and neutrophil infiltration. PRCV infection was asymptomatic and produced a mild bronchointerstitial pneumonitis and neutrophil infiltration (13 to 22 per cent of BAL cells at 4 d PI). IFN -alpha titres parallelled those found during SIV infection, TNF -alpha was negligible and IL -1 undetectable. PRRSV infection induced anorexia and lethargy between 3 and 5 d PI. There was marked infiltration with mononuclear cells in alveolar septa and BAL fluids between 7 and 10 d PI, while neutrophils remained at less than 11 per cent of BAL cells at any time. IL -1 was produced from three throughout 10 d PI, while IFN -alpha production was minimal and TNF -alpha undetectable. These data strongly suggest that proinflammatory cytokines can be important mediators of viral respiratory disease.
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PMID:Differential production of proinflammatory cytokines in the pig lung during different respiratory virus infections: correlations with pathogenicity. 1042 40

Between March 1992 and August 1993, thirty patients with hairy cell leukemia (HCL) were treated in a single institution with 2-chlorodeoxyadenosine (2-CdA) for one course (N=27) or two courses at six month interval (N=3). Sixteen patients were previously untreated, 14 had been treated with alpha interferon (alpha IFN) (N=5), alpha IFN and splenectomy (N=8) and splenectomy, alpha IFN and Deoxycoformycin (N=1). Overall results in 29 evaluable patients were: 25 CR (86%), 3 PR (10%), one failure. The three PR patients relapsed after 18, 24 months and five years. Two were retreated successfully. Two CR patients relapsed after five years. Careful clinical survey, sequential bone marrow biopsies (BMB) with DBA44 immunostaining for assessment of response and detection of residual disease and serially evaluation of lymphocyte subsets counts were performed. Results of bone marrow biopsies study show 1) a progressive reduction in hairy cell infiltration during the first six months after therapy and not after that indicating that the best moment for the evaluation of response may be the sixth month, 2) the persistence of a very small number of DBA44+ cells (80% of BMB). There was a correlation between the presence of > 5% DBA44 positive cells on 6th month BMB and relapse. 60% had an absolute CD4+ lymphocyte count less than 0.2 10(9)/l at least on one examination after treatment. CD4+ lymphocyte level persisted less than baseline level in 8/18 patients tested after four and/or five years. Lymphopenia was less marked in splenectomized patients: 7/7 splenectomized patients tested have recovered a CD4+ lymphocyte count equal to pretherapy level compared to 3/11 non splenectomized patients (p: 0.004). Three opportunistic infections were observed early (first 6 months) after 2CdA therapy: pneumocystis pneumonia, retinitis due to toxoplasma in the patient who failed and legionella pneumonia in a patient retreated after relapse. Two patients developed a second carcinoma 6 and 12 months after therapy. Five patients died, three from a cause unrelated to HCL, one from HCL and one from infection while in second CR. At five years, overall survival is 83% and progression free survival is 66%. Our study shows 1) long-lasting response in the majority of patients after 2-CdA, 2) a correlation between persistent minimal residual disease detected with DBA44 immunostaining and occurrence of relapse and 3) a profound and persistent CD4+ lymphopenia more marked in non splenectomized patients.
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PMID:Five years follow-up after 2-chloro deoxyadenosine treatment in thirty patients with hairy cell leukemia: evaluation of minimal residual disease and CD4+ lymphocytopenia after treatment. 1060 93

Human parainfluenza virus type 3 (HPIV3) is one of the major causes of bronchiolitis, pneumonia, and croup in newborns and infants. Cellular immunity involving major histocompatibility complex (MHC) class I and class II molecules plays an important role in controlling virus infection. Several viruses have been shown to down-regulate gamma interferon (IFN-gamma)-mediated MHC class II expression. In this communication, we show that HPIV3 strongly inhibits the IFN-gamma-induced MHC class II expression in HT1080 human fibrosarcoma cells. The culture supernatant of HPIV3-infected cells also inhibited IFN-gamma-induced MHC class II expression, a phenomenon that was found to be due, in large part, to alpha/beta interferon (IFN-alpha/beta). Expression of MHC class I and intercellular adhesion molecule 1 occurred efficiently in cells simultaneously infected with HPIV3 and treated with IFN-gamma, indicating that the inhibitory effect of HPIV3 was specific to MHC class II. STAT1 activation was not affected by HPIV3 at early postinfection times but was partially inhibited at later times. These data suggested that the potent inhibition of MHC class II expression was, in major part, due to a defect downstream of STAT1 activation in the IFN-gamma-induced MHC class II expression pathway. Class II transactivator (CIITA) is the unique mediator of IFN-gamma-induced transcription from the MHC class II promoter. By RNase protection analysis, CIITA expression was found to be strongly inhibited in HPIV3-infected cells. The culture supernatant containing IFN-alpha/beta, on the other hand, inhibited MHC class II expression without affecting STAT1 and CIITA expression. These data indicate that HPIV3 inhibits IFN-gamma-induced MHC class II expression primarily by the viral gene products targeting CIITA and additionally by inducing IFN-alpha/beta to target one or more steps further downstream.
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PMID:Human parainfluenza virus type 3 inhibits gamma interferon-induced major histocompatibility complex class II expression directly and by inducing alpha/beta interferon. 1115 85


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