Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eleven leukemia patients who had undergone bone marrow transplants from HLA-A, B, DR genotypically mismatched unrelated donors received FK506 and short-term methotrexate as prophylaxis for graft-versus-host disease (GVHD). Grade III-IV acute GVHD developed in 2 of the patients, and chronic GVHD developed in 4 of the other patients. Adverse drug reaction included reversible nephrotoxicity, hyperglycemia (all patients) and hypertension (9 patients). Hyperglycemia and hypertension of grade 3 or higher occurred mostly in the patients who were on supplemental steroids. However, severe nephrotoxicity was not observed. Complications included cystitis (4 patients), cytomegalovirus colitis (3 patients), Interstitial Pneumonitis (IP) (3 patients), tuberculosis (1 patient), and thrombotic microangiopathy (1 patient). None of patients relapsed. Although close monitoring of FK506 blood concentration and patient clinical signs are required, we concluded that FK506 is effective for GVHD prophylaxis after bone marrow transplantation from HLA-A, B, DR genotypically mismatched unrelated donors, and that adverse reactions due to FK506 are controllable. To determine the long-term effectiveness of this drug, it will be necessary to conduct prospective randomized studies that compare it wiht cycloporin A as a preventive treatment against GVHD in patients who receive bone marrow transplants from HLA genotypically mismatched unrelated donors.
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PMID:[FK506 for the prophylaxis of graft-versus-host-disease after bone marrow transplantation from HLA-genotypically mismatched unrelated donor]. 978 75

To study the mechanisms underlying the development of interstitial pneumonia in autoimmune disease, we analyzed bronchoalveolar lavage fluid (BALF) in an animal model of interstitial pneumonia in which an intratracheal instillation of staphylococcal enterotoxin B (SEB) induced interstitial pneumonia in autoimmune-prone mice. Increases in the numbers of total cells, macrophages, lymphocytes, and neutrophils were observed in BALF from SEB-treated MRL +/+ mice, and peaked at 3 d after SEB administration (Day 3). Flow cytometric analyses revealed increases in SEB-reactive Vbeta8(+) T cells, indicating that SEB-reactive cells play an important role in bronchoalveolar space. The expressions of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, JE/monocyte chemoattractant protein-1, regulated on activation, normal T cells expressed and secreted, and KC/gro messenger RNA (mRNA) in BALF cells from SEB-treated mice peaked at Day 3. Increased expression of TNF-alpha mRNA was observed mainly in macrophages and CD8(+) T cells, and the increase in IFN-gamma mRNA was observed mainly in CD8(+) T cells in BALF at Day 3. The expression of platelet-derived growth factor mRNA was very weak at Day 3 but strongly expressed at Day 14. An immunosuppressant, FK506, but not corticosteroid, suppressed SEB-induced T-cell expansion in BALF as well as increased cytokine and chemokine production in the bronchoalveolar space of SEB-treated mice. Histologically, FK506 but not corticosteroid significantly reduced both the cell infiltration to alveolar septal walls and the synthesis of pulmonary collagen fibers. Further, transfer of T cells of MRL +/+ mice with SEB into SCID mice gave rise to interstitial pneumonia. These results suggest that superantigen-reactive T cells in the bronchoalveolar space may trigger the development of interstitial pneumonia in this model.
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PMID:Role of T cells in bronchoalveolar space in the development of interstitial pneumonia induced by superantigen in autoimmune-prone mice. 1057 64

Asthma is orchestrated by cytokine products of activated T cells. Glucocorticoids are thought to ameliorate asthma at least partly through T cell inhibition. Consequently, other T cell immunomodulatory agents have been assessed for asthma therapy. Since these agents may have serious unwanted effects, attention has been focused on patients with severe asthma refractory to maximal topical, and additional systemic glucocorticoid therapy. Although gold salts show a modest but significant glucocorticoid-sparing effect in severe asthma, lung function is not improved and not all patients respond. The minimum duration of a valid trial of therapy is probably 6 months. Unwanted effects include dermatitis, hepatic dysfunction, proteinuria and interstitial pneumonitis. Meta-analysis of trials of methotrexate in oral glucocorticoid-dependent asthma have confirmed that concomitant weekly methotrexate for a minimum of 3 to 6 months enables significant (approximately 20%) overall reduction in oral glucocorticoid requirements, although only approximately 60% of patients show a significant response. There is little effect on lung function. Blood count and liver function must be monitored. Opportunistic infection is rare but potentially fatal. Cyclosporine, administered for at least 3 months, is effective in only a proportion of patients with oral glucocorticoid-dependent asthma, where it may improve disease severity and/or enable oral glucocorticoid dosage reductions. Regular monitoring of renal function, blood pressure and blood concentrations of cyclosporine is required. The evidence that intravenous immunoglobulin (Ig) is of any benefit in patients with glucocorticoid-dependent asthma is at present equivocal. The therapy is expensive and associated with a high incidence of unwanted effects (fever, aseptic meningitis, urticaria). The macrolides tacrolimus (FK506) and sirolimus (rapamycin) have end effects similar to those of cyclosporine. Brequinar sodium, mycophenolate mofetil and leflunomide are inhibitors of de novo synthesis of pyrimidines and purines, to which T cells are particularly sensitive. Such drugs may in theory be beneficial for therapy of patients with oral glucocorticoid-dependent asthma. Humanized anti-CD4, anti-IgE and anti-interleukin (IL)-5 monoclonal antibodies, and other cytokine inhibitors such as soluble IL-4 receptor have entered early trials. The worth of current immunomodulatory drugs is limited since: (i) not all patients respond, and response cannot be predicted a priori; (ii) the high incidence of unwanted effects makes it difficult to assess overall benefit/risk ratios; (iii) there is increased risk of opportunistic infection and (theoretically) neoplasia; (iv) there are many relative and absolute contraindications to therapy; and (v) there is lack of knowledge about the long-term effects, beneficial or otherwise, of therapy.
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PMID:Asthma refractory to glucocorticoids: the role of newer immunosuppressants. 1472 75