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 in vivo importance of class I MHC regulation of the Tc response to a natural pathogenic agent of high virulence was studied on the basis of our previous demonstration of a major difference in the capacity to generate a Sendai virus-specific Tc response between C57BL/6 (B6, H-2b) mice and H-2Kb mutant B6.C-H-2bm1 (bm 1) mice. These two mouse strains differ from each other only in three amino acids in the crucial H-2Kb restriction element for this response. bm 1 mice, in contrast to B6 mice, are Tc nonresponders against this virus, but show Sendai-specific T cell proliferation, antibody production, and DTH reactions, as well as NK cell activity, equal to those of B6 mice. B6, Sendai Tc-deficient bm 1 and T cell-deficient B6 nu/nu mice differ from each other in susceptibility to lethal pneumonia induced by i.n. inoculation of virulent Sendai virus. The lethal dose (LD50) in B6 mice averaged 152 TCID50, in bm 1 mice, 14 TCID50 and in B6 nu/nu mice 0.5 TCID50. The importance of Tc was also shown by the complete protection of B6 nu/nu mice against infection with a lethal virus dose by i.v. injection of a Sendai virus-specific, IL-2-dependent and H-2Kb-restricted B6 Tc clone. In vivo protection by this Tc clone was H-2Kb-restricted. Apart from Tc, an important role for virus-specific Th cells is evident from the difference in susceptibility between bm 1 and B6 nu/nu mice. This conclusion was supported by the demonstration that the mean survival time of B6 nu/nu and bm 1 nu/nu mice could be significantly prolonged, in an I-Ab-restricted manner, by the injection of in vitro-propagated, Sendai-specific B6 or bm 1 Th clones after a lethal dose of Sendai virus, and by the demonstration that inoculation of these Th clones provided help to virus-specific Tc by means of IL-2 production. Strikingly, Th and Tc cooperate in anti-Sendai virus immunity, since permanent survival of lethally infected nu/nu mice was only achieved by inoculation of a mixture of Tc and Th clones or a mixture of a Tc clone and rIL-2. This study provides a unique model for the study of MHC-disease associations.
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PMID:Cooperation between cytotoxic and helper T lymphocytes in protection against lethal Sendai virus infection. Protection by T cells is MHC-restricted and MHC-regulated; a model for MHC-disease associations. 301 21

We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that in vivo application of recombinant human IL-2 (rhIL-2) can enhance the antiviral effect of a limited number of CD8+T lymphocytes, not only in prophylaxis, but also in therapy, when virus has already colonized host tissues. The observed net effect of IL-2 was consistent with the assumption of daily effector population doublings. The prospects for IL-2-supported immunotherapy of established CMV infection depend upon the tissues involved in disease. It appears that the prospects for controlling established CMV adrenalitis are less promising than for a therapy of interstitial CMV pneumonia.
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PMID:In vivo application of recombinant interleukin 2 in the immunotherapy of established cytomegalovirus infection. 302 72

In order to elucidate the role played by alveolar cytokines in the pathogenesis of HIV-related lung damage, levels of interleukin (IL) 1 beta, IL-2, IL-6, tumor necrosis factor (TNF)-alpha, and interferon (Ifn) were assessed on supernatant of bronchoalveolar lavage fluid from 30 consecutive HIV-1 seropositive (HIVAb+) patients with clinical and radiologic evidence of pneumonia, from 20 HIV- seronegative (HIVAb-) patients with pulmonary sarcoidosis, and from 10 HIVAb- healthy control subjects. Cytokine levels were expressed as picogram (IL-1, TNF), nanogram (IL-6), and international unit (IL-2, Ifn) per milligram of albumin per deciliter. Total and differential cell counts, cytofluorimetric enumeration of CD3+, CD3+/DR+, CD4+, CD8+, and CD8+/CD16+ cells, as well as microbiologic investigations for opportunistic agents were performed on lavage pellets. HIV-related pneumonia was characterized by higher mean alveolar level of IL-2 (12 +/- 5 IU), and by more elevated mean counts of T cells (109 +/- 16), activated T cells (60 +/- 12), and CD8+ cells (90 +/- 13)/microliters if compared with both active sarcoidosis and control subjects, where respective values of 0.2 +/- 0.1 and 0.3 +/- 0.2 IU IL-2/mgAlb/dl, of 52 +/- 11 and 7 +/- 2 T cells, of 20 +/- 5 and 1.2 +/- 0.3 activated T cells, and of 11 +/- 2 and 3 +/- 0.6 CD8+ cells per microliter were found. HIV-infected patients with opportunistic lung infections (OIs) showed the highest mean IL-2 level (21 +/- 4 IU), and higher counts of both CD8+ (117 +/- 20) and CD8+/CD16+ (36 +/- 7) cells per microliter if compared with patients without evidence of OIs (respectively, 62 +/- 13 CD8+ and 18 +/- 3 CD8+/CD16+ cells per microliter). By contrast, extremely high IL-1 levels (1,463 +/- 760 pg), and IL-2 levels similar to control subjects (3.4 +/- 1.2 IU), were found in the absence of OIs. Different mechanisms depending respectively on IL-2-mediated cytotoxic cell recruitment and activation, or IL-1-mediated tissue injury may account for HIV-related lung damage, depending on the presence or absence of opportunistic agents.
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PMID:Alveolar immune mediators in HIV-related pneumonia. Different role of IL-2 and IL-1 in inducing lung damage. 767 46

A 16-year-old girl with refractory AML received unmanipulated BMT from an unrelated donor. Leukemia relapse occurred 82 days later. The patient was then treated with IL-2 1.8 x 10(6) U/m2 for 5 days per week and 2.5 MU/m2 IFN-alpha three times per week. Toxicities included fever, skin rash, somnolence and a generalized seizure. Treatment was stopped after 2 weeks. Acute GVHD developed at the end of therapy and the patient's leukemia went into remission. She died of fungal pneumonia 30 days later. We conclude that a combination of cytokines may be useful in treating relapsed leukemia after BMT.
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PMID:Treatment of leukemia relapse after bone marrow transplantation with interferon-alpha and interleukin 2. 777 25

Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In the present study we investigated the distribution of leukocytes, lymphocyte subsets, their activation state, and the cytokine profile present in BAL fluid from patients with various lung diseases associated with eosinophilia. For this purpose, we analyzed the levels of IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, as well as soluble IL-2 and TNF receptors, in concentrated bronchoalveolar lavage (BAL) fluid obtained from clearly defined patients with allergic and nonallergic asthma, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. BAL fluid from normal individuals and sarcoidosis patients was analyzed as noneosinophilic controls. BAL cytokine levels were compared with the cellular infiltrate and the activation state of CD4+ and CD8+ T cells as measured by the expression of IL-2 receptors (CD25), HLA-DR, and the very late activation antigen VLA-1. Beside the characteristic leukocyte infiltrate in the various lung diseases, all patients demonstrated significantly increased numbers of activated CD4 and CD8 T cells compared with normal individuals. The analysis of the cytokine profile present in BAL fluid revealed a T helper type 2 (Th2) cell cytokine pattern, with elevated IL-4 and IL-5 but normal levels of IL-2 or IFN-gamma in allergic asthma. ABPA patients demonstrated significantly increased levels of IL-4 and IL-5, with low but significantly elevated concentrations of IL-2 and IFN-gamma. In contrast, the analysis of the cytokine profile in sarcoidosis patients revealed a Th1 cell cytokine pattern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5. All other patient groups showed a cytokine pattern incompatible with a pure Th1 or Th2 cell response, because IL-5, IL-2, and IFN-gamma were found to be significantly increased. The BAL fluid analysis of the other, mainly non-T cell-derived cytokines and soluble receptors showed increased levels in all patients compared with normal individuals and may represent the ongoing inflammatory responses. In conclusion, whereas increased IL-4 levels were found only in diseases characterized by increased IgE production, IL-5 was elevated in all patients with increased numbers of eosinophils. The close correlation between IL-5 levels, number of eosinophils, and activated T cells further supports a role for IL-5 in causing tissue eosinophilia.
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PMID:Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. 792 34

Cytokine production has been assessed at the single-cell level (ELISPOT assay) for freshly isolated mediastinal lymph node cells from C57BL/6 mice with primary, nonfatal influenza pneumonia. The mediastinal lymph node populations were also secondarily stimulated in vitro, and culture supernatants were assayed by enzyme-linked immunosorbent assay. Both approaches showed minimal evidence of protein secretion for interleukin-4 (IL-4), IL-5, and tumor necrosis factor, while IL-2, IL-10, and gamma interferon (IFN-gamma) were prominent throughout the response. The numbers of IL-2- and IFN-gamma-producing cells were maximal at 7 days after infection, while the total counts for cells secreting IL-10 were fairly constant from day 3 to 7. The cultures that were stimulated with virus in vitro showed in inverse relationship between IL-10 and IFN-gamma production, with IL-10 peaking on day 3 and IFN-gamma peaking on day 7. Lymphocytes secreting IL-2, IL-10, and/or IFN-gamma were present in CD4+ and CD8+ populations separated by fluorescence-activated cell sorting, although the CD8+ T cells produced less cytokine and were at a relatively lower frequency. Addition of recombinant IL-10 to the virus-stimulated cultures decreased the amount of IFN-gamma that could be detected, while incorporation of a monoclonal antibody to IL-10 had the opposite effect. A neutralization experiment also indicated that IL-2 was the principal mediator of lymphocyte proliferation. These experiments thus show that the developing T-cell response in the regional lymph nodes of mice with influenza cannot be rigidly categorized on the basis of a TH1 or TH2 phenotype and suggest possible regulatory mechanisms.
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PMID:Concurrent production of interleukin-2, interleukin-10, and gamma interferon in the regional lymph nodes of mice with influenza pneumonia. 815 76

The patterns of cytokine mRNA expression in mice with primary or secondary influenza pneumonia have been assessed by in situ hybridization analysis of cells from both the mediastinal lymph node (MLN) and the virus-infected lung. Evidence of substantial transcriptional activity was found in all lymphocyte subsets recovered from both anatomical sites. The kinetics of cytokine mRNA expression after primary infection with an H3N2 virus were in accord with the idea that the initial response occurs in regional lymphoid tissue, with the effector T cells later moving to the lung. This temporal separation was much less apparent for the more rapid secondary response resulting from challenge of H3N2-primed mice with an H1N1 virus. Among the T cell receptor alpha/beta+ subsets, transcripts for interferon (IFN) gamma and tumor necrosis factor beta were most commonly found in the CD8+ population whereas mRNA for interleukin (IL) 4 and IL-10 was much more prevalent in CD4+ T cells. The gamma/delta T cells expressed mRNA for all cytokines tested, with IL-2, IL-4, and IFN-gamma predominating among those recovered from the inflammatory exudate. At particular time points, especially early in the MLN and late in the infected lung, the frequency of mRNA+ lymphocytes was much higher than would be expected from current understanding of the prevalence of virus-specific precursors and effectors. If this response is typical, induction of cytokine gene expression for T cells that are not responding directly to the invading pathogen may be a prominent feature of acute virus infections.
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PMID:Activation of cytokine genes in T cells during primary and secondary murine influenza pneumonia. 842 16

Chronic eosinophilic pneumonitis (CEP) is characterized by longstanding respiratory symptoms accompanied by a massive pulmonary eosinophil infiltration. We hypothesized that cytokine(s) produced in the disease sites are implicated in the pathophysiology of CEP. We studied peripheral blood and bronchoalveolar lavage fluids (BALF) obtained from two lung segments of a patient with CEP. Seventy times more eosinophils were found in the BALF from an involved lung segment (showing patchy opacification on a chest roentgenogram) than from an uninvolved segment. The eosinophil-active cytokines interleukin-5 (IL-5), IL-6, and IL-10 were strikingly elevated in the BALF from the involved lung segment, whereas no or minimal levels of these cytokines were detectable in the BALF from the uninvolved segment or serum, respectively. Leukocytes in the involved lung segment, but not those in peripheral blood, expressed messenger ribonucleic acid (mRNA) for IL-5, IL-6, and IL-10. In contrast, IL-2, IL-3, IL-4, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) were not detected in any sample. These findings suggest that increased production of several cytokines, such as IL-5, IL-6, and IL-10, in the involved lung segment, but not in the uninvolved lung segment or peripheral blood, is a critical pathophysiologic feature of CEP.
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PMID:Cytokine production at the site of disease in chronic eosinophilic pneumonitis. 861 78

The success of autologous stem cell transplantation (ASCT) for hematologic malignancy is limited largely by a high relapse rate. It is postulated that IL-2 administered after ASCT may eliminate minimal residual disease and thereby reduce relapses. A phase I/II study was performed to identify a regimen of IL-2 (Chiron) that could be given early after ASCT in phase III trials. In the phase I study, beginning a median of 46 days after ASCT for hematologic malignancy, cohorts of three to four patients received escalating doses of 'induction' IL-2 of 9, 10, or 12 x 10(6) IU/m2/day for 4 or 5 days by continuous i.v. infusion (CIV), followed by a 4-day rest period, and then 1.6 x 10(6) IU/m2/day of maintenance IL-2 by CIV for 10 days. The maximum tolerated dose (MTD) of induction IL-2 was 9 x 10(6) IU/m2/day x 4. In the phase II study, 52 patients received the MTD. Eighty percent of patients completed induction IL-2. Most patients exhibited some degree of capillary leak. One patient died of CMV pneumonia and one died of ARDS. Maintenance IL-2 was well tolerated. In the phase I/II study, 16 of 31 patients with non-Hodgkin lymphoma (NHL), 3/8 with Hodgkin disease (HD), 4/17 with AML, and 4/5 with ALL remain in CR. Two of six multiple myeloma (MM) patients remain in PR. Although the regimen of IL-2 identified had significant side-effects in some patients, it was well tolerated in the majority of patients. Phase III prospectively randomized clinical trials are in progress to determine if this IL-2 regimen will decrease the relapse rate after ASCT for AML and NHL.
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PMID:Interleukin-2 after autologous stem cell transplantation for hematologic malignancy: a phase I/II study. 905 8

4 wk after intraperitoneal inoculation of 0.2 LD50 (50% lethal dose) of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable in the salivary glands, but not in the lungs or other organs. When the T cells of these mice were activated in vivo by a single injection of anti-CD3 monoclonal antibody, interstitial pneumonitis was induced in the lungs that were free of the virus with an excessive production of the cytokines. In the lungs of such mice persistently infected with MCMV, the mRNA of the cytokines such as IL-2, IL-6, TNF-alpha, and IFN-gamma were abundantly expressed 3 h after the anti-CD3 injection, and the elevated levels continued thereafter. A marked expression of inducible nitric oxide synthetase (iNOS) was then noted in the lungs, suggesting that such cytokines as TNF-alpha and IFN-gamma may have induced iNOS. Although the increase in NO formation was demonstrated by the significant elevation of the serum levels of nitrite and nitrate, the interstitial pneumonitis was not associated with either increased superoxide formation or peroxynitrite-induced tyrosine nitration. Nevertheless, the administration of an NO antagonist also alleviated the interstitial pneumonitis provoked by anti-CD3 mAb. Based on these findings, it was concluded that MCMV-associated pneumonitis is mediated by a molecule of cytokine-induced NO other than peroxynitrite.
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PMID:Nitric oxide mediates murine cytomegalovirus-associated pneumonitis in lungs that are free of the virus. 931 83


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