Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The T cell-derived macrophage-activating lymphokine, interferon-gamma (IFN-gamma), is the most broadly acting antimicrobial-inducing and host defense-enhancing cytokine thus far identified in experimental models of infectious diseases. The activity induced by IFN-gamma encompasses all classes of non-viral pathogens including intracellular and extracellular parasites, fungi and bacteria. In man, treatment with immuno-enhancing doses of IFN-gamma is safe, well-tolerated and stimulates the antimicrobial mechanisms of blood monocytes, circulating neutrophils and tissue macrophages. Aerosol administration activates alveolar macrophages in a compartmentalized fashion. Monocytes from IFN-gamma-treated patients with cancer, leprosy, and AIDS all respond with the activated phenotype, and suppressed monocyte HLA-DR expression in trauma patients can be up-regulated by IFN-gamma therapy. Thus far, IFN-gamma has been recognized as effective in the prophylaxis of chronic granulomatous disease and as adjunctive treatment in at least one systemic intracellular infection, visceral leishmaniasis. Additional trials suggest beneficial effects as prophylaxis in trauma and as treatment in leprosy, cutaneous leishmaniasis, and HIV- and non-HIV-related disseminated atypical mycobacterial infection. IFN-gamma is also being tested as a prophylaxis in patients with burns and advanced HIV infection and as an adjunct in drug-resistant tuberculosis. Future antimicrobial applications for IFN-gamma include: a) long-term prophylaxis in T cell-deficient states, b) short-term prophylaxis in patients with a reversible host defense defect such as granulocytopenia or immune response suppression induced by trauma or burn injury, and c) adjunctive treatment along with conventional antibiotic therapy for i) nosocomial pneumonia (aerosol administration), ii) opportunistic infections in general, iii) infections which typically respond poorly to available treatment and iv) for infections which require prolonged therapy for cure. In the latter, the addition of IFN-gamma may accelerate the response to conventional therapy and permit a clinically important reduction in the duration of treatment while preserving efficacy.
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PMID:Current and future clinical applications of interferon-gamma in host antimicrobial defense. 892 89

In patients with cystic fibrosis (CF), respiratory tract infections caused by Staphylococcus aureus and Haemophilus influenzae are followed by Pseudomonas aeruginosa with increasing age. Chronic endobronchial lung infection with P. aeruginosa is the leading cause of morbidity and mortality. In Danish CF patients we noted that both onset of initial colonization and chronic lung infection with P. aeruginosa peaked during the winter months which is the season for respiratory virus infections. Virus may therefore pave the way for P. aeruginosa. We established a chronic P. aeruginosa lung infection in rats by embedding mucoid bacteria in seaweed alginate and installing the beads intratracheally into the lower part of the left lung. Although the rats did not suffer from CF, the antibody responses and the pathologic changes of the lungs mimicked the findings in CF patients. By using this model in normal and athymic rats we showed that the T-cell response during the "natural" course of the infection played no major role. In a model of acute P. aeruginosa pneumonia we found that the macroscopic inflammatory response of the lungs was immense and that the natural capacity to clear P. aeruginosa was very efficient and could not be improved by immunization, although high serum levels of IgM, IgG and IgA antibodies to P. aeruginosa alginate, LPS, exotoxin A and sonicate were induced. We developed a method for collecting and measuring IgA in saliva and noted that mucosal IgA antibodies were induced by vaccination; they did not significantly prevent inflammation, however. In the chronic rat model we succeeded to improve the survival significantly and to change the inflammatory response subsequent to vaccination from an acute type inflammation dominated by polymorphonuclear leukocytes (PMNs) as in CF patients to a chronic type inflammation dominated by mononuclear leukocytes. Furthermore, we found that rats immunized with an alginate containing vaccine had a significantly earlier cellular shift to a chronic type inflammation as well as a significant reduction in the severity of the macroscopic inflammation compared to two other vaccine groups and to nonimmunized controls. Similar results were obtained in rats treated with the TH1 cytokine, interferon-gamma (IFN-gamma). Several authors have shown that the lung tissue damage during chronic infection in CF patients is caused by a type III hypersensitivity reaction leading to release of elastase by PMNs surrounding the bacterial microcolonies. The cellular shift we have induced by vaccination and by IFN-gamma treatment therefore offers a possible new strategy for improving the clinical course in chronically infected CF patients.
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PMID:Potential of preventing Pseudomonas aeruginosa lung infections in cystic fibrosis patients: experimental studies in animals. 894 52

A Th1-type response develops following vaginal infection with the mouse pneumonitis biovar of Chlamydia trachomatis (MoPn). Since the type of response, i.e., Th1 versus Th2, can be influenced by factors present during T-cell activation, we examined the effects of different routes of MoPn administration on the cytokine profile and resistance against infection following a MoPn vaginal challenge. A dominant Th1-type cytokine profile developed in mice given live MoPn via the intranasal, oral, and vaginal routes with ratios of gamma interferon-secreting cells to interleukin 4-secreting cells greater than 10. In contrast, mice injected subcutaneously produced a Th2-type profile with a gamma interferon/interleukin 4 ratio of only 0.7. These mice also had significantly higher anti-MoPn immunoglobulin G1 serum titers, confirming a Th2-type cytokine profile. Exposure of mice to live MoPn, by any route prior to vaginal challenge, resulted in a shortened course of infection. However, the subcutaneous group resolved the vaginal infection more slowly, with 60% (6 of 10 mice) of the mice still isolation positive 12 days after challenge compared with only 20% of mice given live MoPn by other routes. Administration of UV-inactivated MoPn did not provide protection against a vaginal challenge. The decreased ability to clear infection was not associated with a shift in the cytokine profile, since intranasal and oral administration of UV-inactivated MoPn resulted in a predominant Th1-type response. Taken together, these data indicate that the initial route of MoPn administration can direct the type of response produced after a local MoPn infection and thus influence the ability of the immune response to protect against subsequent infection.
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PMID:Initial route of antigen administration alters the T-cell cytokine profile produced in response to the mouse pneumonitis biovar of Chlamydia trachomatis following genital infection. 894 35

The increasing challenge posed by multiresistant saprophytes in medical microbiology is strikingly demonstrated by the emergence of Burkholderia (formerly Pseudomonas) cepacia as an opportunist pathogen in immunocompromised patients, particularly individuals with chronic granulomatous disease and cystic fibrosis (CF). Best known previously as a phytopathogen and the cause of soft rot of onions, B. cepacia presents three major problems for the CF community: innate multiresistance to antimicrobial agents; person-to-person transmission of epidemic strains through nosocomial or social contacts; and 'cepacia syndrome', a fulminating fatal pneumonia, sometimes associated with septicaemia, that occurs in approximately 20% of colonised patients, including those with previously mild disease. Accumulated evidence to dispel earlier suggestions that the organism is avirulent and merely a marker of existing lung disease includes: case-controlled studies in CF patients; reports of serious infections in non-CF patients; in-vitro and in-vivo evidence that B. cepacia induces production of pro-inflammatory markers, including the major cytokine TNFalpha; and histopathological evidence that exposure of transgenic CF mice to B. cepacia results in pneumonia. By the early 1990s, the use of selective culture media and DNA-based bacterial fingerprinting confirmed suspicions of epidemic person-to-person spread of B. cepacia. This evidence provided scientific justification for draconian and controversial measures for infection control, in particular, segregation of B. cepacia-colonised patients during treatment at CF centres and their exclusion from social gatherings and national conferences. Recently, molecular analyses of type strains and clinical isolates have revealed that isolates identified previously as B. cepacia belong to at least three distinct species and have increased concern regarding the reliability of current laboratory detection and identification systems. Clarification of the taxonomy of B. cepacia-like organisms and the pathogenic potential of environmental isolates remains a high priority, particularly when the organism's antifungal and degradative properties have created interest in its potential use as a biological control agent to improve crop yields and its use for the bioremediation of contaminated soils.
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PMID:Burkholderia cepacia: medical, taxonomic and ecological issues. 895 42

Despite improvements in immunosuppression, rejection occurs in 50% of liver transplant patients and may cause significant morbidity. The most frequent cause of death after liver transplantation is severe infection. Determination of the cytokine network may lead to earlier detection of patients at risk for severe rejection and infection. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines and neopterin on a daily basis. During the first postoperative month, 28 patients (34.6%) developed acute rejection; 14 patients were successfully treated with methylprednisolone (steroid-sensitive rejection), while 14 patients required additional treatment with FK506 and OKT3 (steroid-resistant rejection). Ten patients developed severe infections, and 11 patients experienced asymptomatic cholangitis. Patients with an uneventful postoperative course (n=37) were the control group. One-year patient survival was 88.9%: 1 patient died because of chronic rejection and Pseudomonas urosepsis; a further 4 patients died of aspergillus pneumonia and bacterial sepsis. Soluble TNF-RII, sIL-2R-, and IL-10 levels were significantly elevated 3 days prior to or at the onset of acute steroid-resistant rejection (P < or = 0.01 versus steroid-sensitive rejection and on uneventful postoperative course). An increase in IL-8, neopterin, and sTNF-RII was indicative of severe infection 3 days prior to onset of infection. In this group of patients, a simultaneous increase in IL-10 indicated a lethal outcome of severe infection. During the second week of acute steroid-resistant rejection and lethal infection, a significant rise in IL-1beta, IFN-gamma, and IL-6 was observed (P < or = 0.01 versus control groups). The different patterns in neopterin- and cytokine-increase could differentiate between severe rejection and severe infection. Furthermore, the increase in these parameters indicated severe rejection--i.e., steroid resistance at the onset of acute rejection--which could prompt us to initiate rescue therapy immediately. The ability to detect patients at risk for severe or lethal infection may result in intensified infectious screening and more aggressive antiinfectious treatment. Therefore, routine monitoring of these parameters may lead to changes in therapeutic management of severe acute rejection and infection after liver transplantation.
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PMID:Cytokine pattern during rejection and infection after liver transplantation--improvements in postoperative monitoring? 895 70

Because of an increasing number of patients suffering from Leishmania infections and because of the serious consequences of these infections more thorough knowledge of the host factors responsible for resistance and susceptibility to the diseases is needed. In murine models of Leishmania infections the cytokine production by CD4+ T cells has been identified as a major factor in determining the outcome of the infection. In these models Th1 cells producing IFN-gamma provide protection against the infection whereas Th2 cells producing IL-4 and IL-10 aggravate the disease. The fatal outcome of Leishmania infections in humans with defects in T-cell functions illustrates that these cells are fundamental in the defence against Leishmania in humans also. However, as for many other infectious diseases (meningococcal disease and other septicaemic conditions, pneumonia, viral hepatitis, schistosomiasis) the immune reactions to Leishmania parasites in humans can be associated with both protection and pathogenesis. Many individuals without previous exposure to Leishmania parasites have T cells which can respond to Leishmania antigens. These cells have the potential to generate either Th1 or Th2 like responses. During infection with Leishmania parasites humans develop specific T-cell recognition of well-characterized parasite antigens. T cells producing disease-exacerbating factors such as IL-4 in response to Leishmania antigen stimulation have been identified in humans as well as in mice. Both Th1 like and Th2 like cells recognizing Leishmania antigens can be expanded during infection. At the polyclonal level Th1 like responses to Leishmania antigens are found in individuals who have had self-healing or asymptomatic infections. Factors secreted by such Leishmania specific Th1 like cells can induce killing of intracellular parasites in infected macrophages. In individuals who have been cured from uncontrollable disseminating disease both Th1 and Th2 like responses can be detected. A restriction in the antigen recognition to particular protein fractions could not be demonstrated in the Th1 or Th2 like responses. These findings suggest an association between the pattern of cytokines produced by parasite specific T cells and the clinical course of the infection similar to the one seen in mice. In the murine model the cytokine pattern present in the animal at the time of infection can determine whether a Th1- or a Th2 response will develop. In vitro studies on human and murine cells have confirmed that certain cytokines (e.g. IFN-gamma, IL-12) will favour maturation of Th1 responses whereas others (e.g. IL-4, IL-10) support Th2 development. If similar immunoregulatory mechanisms operate in mouse and man, design of vaccines against human leishmaniasis should aim at introducing powerful Th1 like responses. Importantly, once generation of either Th1 or Th2 has started, the immune response seems to be locked in this pattern, even when it is harmful to the host. Therefore new vaccines against leishmaniasis should be designed in a way that they generate controlled Th1 like primary responses.
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PMID:Regulator and effector functions of T-cell subsets in human Leishmania infections. 906 93

Interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) levels in 20 patients with bacteremic Streptococcus pneumoniae community-acquired pneumonia (CAP) were compared with these cytokine levels in 20 patients with Mycoplasma pneumoniae CAP. All 40 patients survived hospitalization and underwent a follow-up examination one month later. Serum IL-1beta and IL-6 levels were determined by the enzyme immunoassay (EIA) method using commercial kits. In the acute phase of CAP, IL-6 levels were significantly higher in the S. pneumoniae group (p = 0.014), while IL-1beta levels were higher in the M. pneumoniae group (p = 0.046). In the convalescence phase, the two cytokines were detected in a considerable number of patients in both groups. In this phase, only the level of IL-1beta was significantly higher in the M. pneumoniae group than in the S. pneumoniae group (p = 0.03). We conclude that the levels of IL-1beta and IL-6 are different between patients with S. pneumoniae-CAP and M. pneumoniae-CAP during the acute phase. In the convalescence phase, cytokine levels remain high in some of the CAP patients, but a significant difference between the groups exists only for IL-1beta. Further studies are required.
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PMID:IL-1beta and IL-6 in community-acquired pneumonia: bacteremic pneumococcal pneumonia versus Mycoplasma pneumoniae pneumonia. 910 83

To evaluate whether concentrations of cytokines supposed to be involved in eosinophil recruitment and activation were elevated in cystic fibrosis (CF), we assessed interleukin-3 (IL-3), IL-5, IL-8, regulated on activation, normal T-cell expressed and secreted (RANTES); and granulocyte-macrophage colony stimulating factor (GM-CSF) in sputa from 32 patients with CF, eight patients with atopic bronchial asthma, and six patients with bacterial pneumonia. In addition, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as markers of eosinophil activation. In patients with CF, sputum levels of IL-8 were elevated (p < 0.01) as compared with asthmatic patients. Concentrations of IL-3, ECP, and EPX were not different in the two groups. However, IL-5 (p < 0.0001), RANTES (p < 0.003), and GM-CSF (p < 0.0001) were significantly lower in the CF group than in subjects with asthma. IL-5 was detected only in sputum samples from CF patients with Aspergillus sensitization. In patients with pneumonia, IL-8 levels only were increased. In CF sputum, ECP levels were significantly correlated with the levels of IL-8 (r = 0.626, p < 0.0001) and IL-3 (r = 0.642; p < 0.0001), whereas in asthmatic patients IL-5, IL-8, and RANTES concentrations were significantly related to ECP in sputum. These findings suggest that different cytokine profiles are responsible for eosinophil activation in patients with CF as compared with asthmatic patients. In CF, IL-8 and IL-3 appear to be responsible for increased degranulation of eosinophils.
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PMID:Cytokine concentrations in sputum from patients with cystic fibrosis and their relation to eosinophil activity. 911 85

Interleukin-6 (IL-6), among other cytokines, is thought to be involved in the regulation of sickness behavior (e.g., anorexia, cachexia, fever, and lethargy) induced by infections bacterial and viral origin) and sterile tissue necrosis (burns and surgical traumas). Mice deficient in IL-6 (IL-6 KO) were generated by gene targeting. Homozygous IL-6 KO male and female mice and their appropriate controls were implanted with biotelemeters to monitor body temperature (Tb) and motor activity (Act). Normal circadian rhythms in Tb and Act as well as rates of food intake and weight gain did not differ significantly between sex-matched IL-6 KO and control groups at 30 degrees C in a 12:12-h light-dark cycle. Sterile tissue damage was induced in mice by subcutaneous injection of turpentine (0.1 ml, left hindlimb). Influenza pneumonitis was induced by intranasal inoculation of mouse-adapted influenza A virus (17.5 plaque-forming units). Lack of IL-6 completely prevented fever, anorexia, and cachexia because of turpentine abscess in both sexes. It did not prevent lethargy, although IL-6 KO mice recovered to normal Act significantly sooner than wild-type mice. Symptoms of sickness were only slightly modified during influenza virus infection in IL-6 KO mice. Attenuation of sickness behavior was more pronounced in IL-6 KO female than in male mice. We conclude that, although IL-6 is induced during both turpentine abscess and influenza infection, this cytokine appears to be more critical in induction of the symptoms of sickness behavior during sterile tissue abscess than during influenza infection.
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PMID:Sickness behavior in mice deficient in interleukin-6 during turpentine abscess and influenza pneumonitis. 912 87

Alveolar macrophages (AM), which represent the major resident population of immunocompetent cells in the lower respiratory tract, have been implicated in the pathogenesis of acute lung injury in view of their exceptional capacity to release a large array of inflammatory mediators. The ex vivo analysis of these cells, accessible to bronchoalveolar lavage (BAL) is hampered by the fact that, under conditions of respiratory failure, the AM pool is heavily expanded by polymorphonuclear neutrophils (PMN), which necessitates separation of these cell populations. In the present study, we describe a flow cytometric approach to sort human AM obtained from BAL samples of both healthy volunteers (n = 10) and patients with severe pneumonia demanding mechanical ventilation (n = 10), using forward scatter and high autofluorescence characteristics to discriminate AM from PMN and lymphocytes. This technique yielded highly purified AM populations (>95%) as evidenced by morphological analysis, cytochemistry, and CD71 and CD14 expression of the sorted cells. The flow sorting process, per se, did not induce the expression of the acute-phase cytokine tumor necrosis factor-alpha (TNF-alpha) in control AM as determined by reverse transcriptase-polymerase chain reaction. Unstimulated and lipopolysaccharide-induced TNF-alpha protein secretion were comparable in sorted and unsorted AM as demonstrated by enzyme-linked immunosorbent assay. We suggest flow sorting of viable human AM as an efficient and nonperturbing separation technique to yield highly purified cell populations especially from PMN-rich BAL fluids of critically ill patients.
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PMID:Separation of human alveolar macrophages by flow cytometry. 912 15


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