Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematological effects of tilorone, an interferon inducer, on the hematopoietic cell system of normal CBA/Ca mice and on the development of Friend virus (FV-P)-induced polycythemia in DBA/2 mice were studied. In normal mice 80 mg/kg IP had a marked depressive effect on pluripotent (CFU-s), granuloid committed (CFU-C), and erythroid committed (CFU-E) stem cells with regeneration between days 5 and 12. In bone marrow smears only lymphopenia was detected. Treatment of mice before FV-P infection caused a slight retardation in the development of the splenomegaly and the transformation of bone marrow cells to Ep independence. Repeated treatment after FV-P infection also reduced the increase in spleen weight and the development of reticulocytosis, but the Ep independence of bone marrow and spleen cells was not influenced. In vitro exposure of normal cells and cells from FV-P-infected animals to the drug showed the same sensitivity of colony growth in normal as well as in Ep-independent CFU-E. The action of the drug on Friend leukemia is at least in part considered a toxic effect on the hematopoietic stem cell system.
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PMID:Effects of tilorone on hemopoietic stem cells and on the development of Friend leukemia. 746 Jan 94

Many patients with chronic lymphocytic leukemia (CLL) achieve remission after treatment with fludarabine chemotherapy. Most of these patients, however, later experience relapse. In addition, immunologic deficits may persist even in patients in complete remission; lymphopenia, predominantly involving the CD4 population, is universal after fludarabine therapy. We used recombinant alpha interferon (IFN-alpha) maintenance therapy in patients with CLL who achieved remission in response to fludarabine therapy to determine its effect on residual disease, assessed by either bone marrow biopsy or flow cytometry, and on immune restoration. Thirty-one patients were treated with IFN-alpha (3 x 10(6) U by subcutaneous injection three times weekly). Twenty-two patients (71%) were in complete remission (CR) and nine (29%) were in partial remission (PR). Of the 22 patients in CR, 21 (95%) had evidence of residual disease at the start of IFN-alpha therapy. Low CD4 levels were noted in 93% of patients, low IgG levels in 45%, and anergy or hypoergy in 52%. Only one patient in PR achieved a CR on IFN-alpha therapy: the only patient who had had no prior fludarabine but had been treated with chlorambucil and prednisone. All patients in CR with minimal residual disease had persistent disease after IFN-alpha treatment. There were no increases in CD4 counts or IgG levels; three patients with borderline responses to skin testing had an increase in the number of positive tests while on IFN-alpha. The time to progression was no different in patients treated with IFN-alpha than in a historical control group of patients who had received no further therapy after fludarabine. In summary, the use of IFN-alpha maintenance did not eradicate residual disease, restore immune function, or prolong remissions in patients with CLL responsive to fludarabine.
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PMID:Interferon maintenance therapy for patients with chronic lymphocytic leukemia in remission after fludarabine therapy. 763 36

Recombinant human interleukin-2 (IL-2) was administered by the intravenous (i.v.) or intralymphatic (i.l.) route to 14 patients with advanced malignancy. IL-2 was given in doses of 600,000 IU/kg or 1,050,000 IU/kg daily x 5. Thoracic duct (TD) catheters were placed, and both TD lymphocytes (TDL) and peripheral blood lymphocytes (PBL) were studied. Five of eight patients at the 600,000 IU/kg dose experienced grade III toxicity as did five of six patients at the 1,050,000 IU/kg dose. Two episodes of grade IV toxicity were seen at the higher dose. The i.l. and i.v. routes had a similar toxicity profile excepting lymphangitis/pedal infection, seen only with i.l. administration. One partial response was seen in a patient with renal cell carcinoma. Lymphopenia was seen early in therapy, with lymphocytosis by day 6. Lymphoid yield of the TD catheter fell early in therapy, then increased over baseline by the end of treatment. Intralymphatic administration resulted in a prolonged serum t1/2 and lower serum levels than did i.v. administration, but resulted in higher TD levels. Antibodies against IL-2 were ubiquitous but had no clear effects. Lymphocyte trafficking studies suggested that IL-2 affected lymphocyte redistribution to liver, spleen, bone marrow, and lymph nodes. NK activity and phenotype and LAK activity increased in response to IL-2, with no advantage for TDL. Tumor necrosis factor-alpha and gamma-interferon levels increased sporadically with treatment. The i.l. route offered no advantage over the i.v. route, and TDL offered no advantage over PBL.
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PMID:A comparative study of intravenous versus intralymphatic interleukin-2, with assessment of effects of interleukin-2 on both peripheral blood and thoracic-duct lymph. 813 47

In a great majority of patients with systemic lupus erythematosus (SLE) lymphocytotoxic antibodies (LCA) are detected. The reported prevalence depends on the methods of detection and definition of test-positivity. The pathogenetic role of LCA remains unclear. Different reports show that LCA can have an influence on mononuclear cell function, e.g., on production of interferon, or specifically on T-cell function. In several studies T-cell specificity of LCA cannot be shown. Sometimes an overlap between LCA and anti-B2M antibodies is found, suggesting that LCA have anti-B2M activity. Anti-B2M activity might have an impact on T-cell as well as on B cell function. Next to the anti-B2M activity, binding to nuclear material is claimed. Investigating the role of LCA in respect to lymphopenia, a direct relationship cannot be found; however, LCA might induce interferon production, resulting in lymphopenia. Several studies show or claim a relationship between the presence of LCA and neurological manifestations in SLE patients; the results, however, remain questionable due to the difference in detection methods as well as in definition of central nervous system (CNS) involvement. In other studies, an increased incidence of LCA is reported in relatives of SLE patients as well. In addition, LCA are reported in quite a lot of other diseases such as rheumatoid arthritis, ankylosing spondylitis, malignancies and viral illnesses. This latter association has led to the assumption that LCA might have a virus-related origin.
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PMID:Lymphocytotoxic antibodies in SLE: a review of the literature. 818 40

Domperidone, anti-emetic drug, given to healthy female volunteers, induced an elevation of plasma prolactin (PRL) concentration with the peak in 1-4 h. The release of prolactin had a transient stimulating effect on theophylline sensitive T lymphocytes and on concanavalin A induced mitogenic activity, suggesting an enhanced activity of T suppressor lymphocytes. The relative number of CD4+ lymphocytes decreased markedly one hour after domperidone administration and returned to normal values within 2 h (that means 3 h after taking the drug). The number of lymphocytes positive for dipeptidyl peptidase IV exhibited similar transient increase and normalization of activity. No change was observed in the number of CD8+ lymphocytes. The production of interferon by leukocytes treated with Newcastle disease virus was found to be significantly increased 2 h after domperidone administration. The results suggest that prolactin can selectively stimulate some functions of cellular immunity as well as the release of cytokines (IFN). The present study may contribute to the understanding of the role of the immune system in endogenous hyperprolactinemia.
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PMID:Effect of domperidone-induced hyperprolactinemia on selected immune parameters in healthy women. 874

Imiquimod is an orally active interferon inducer with anti-tumour activity in experimental animals. In this study the tolerability, toxicity and biological effects of daily oral imiquimod administration were investigated in 21 patients with refractory cancer. Patients were treated with doses of 25 mg, 50 mg, 100 mg or 200 mg on a projected 112 day course. Only three patients completed the course, all at the 50 mg dose. Treatment toxicities were dose related and mainly comprised flu-like symptoms, nausea and lymphopenia. Of the 21 patients, five received dose reductions and in five treatment was discontinued because of treatment-related toxicity. The biological activity of imiquimod was confirmed by significant and sustained rises in peripheral blood mononuclear cell (PBMC) 2-5A synthetase (2-5AS) levels at all doses. At 100 mg and 200 mg these occurred within the first 24 h of administration. Levels of neopterin and beta 2-microglobulin (beta 2M) were also significantly elevated when assessed after three weeks' treatment. Interferon production was not demonstrated within the first 24 h of the initial dose but, following repeated doses, ten of the patients developed detectable serum interferon concentrations with a maximum value of 5600 IU ml-1 recorded. Administration of imiquimod did not have any significant effect on serum levels of tumour necrosis factor (TNF) or interleukin 1 (IL-1), nor did it lead to development of detectable levels of antibodies to interferon. One mixed clinical response was observed after 4 weeks' treatment at 100 mg in a patient with renal cell cancer. Daily administration of imiquimod causes activation of the interferon production system but at higher doses results in unacceptable toxicity. Further investigation of imiquimod as an interferon-inducing agent in cancer patients is suggested at either the lower dose levels or employing alternative dosing schedules.
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PMID:A phase I clinical trial of imiquimod, an oral interferon inducer, administered daily. 891 49

Anti-CD3 monoclonal antibody (mAb) OKT3 is immunosuppressive, but causes severe adverse effects during the first administration ("first-dose reaction"). These adverse effects are presumably caused by cytokine release that results from T-cell activation. In vitro, T-cell activation by anti-CD3 mAb requires interaction with monocyte Fc receptors. The Fc receptor for murine IgG1, Fc gammaRIIa, is polymorphic. In some individuals, murine IgG1 anti-CD3 mAb causes T-cell proliferation and cytokine release in vitro (high responders [HR]), whereas in individuals with the low-responder (LR) phenotype it does not. We have now investigated the role of this Fc gammaRIIa polymorphism in the release of cytokines in vivo and the occurrence of adverse effects after the administration of WT31, a murine IgG1 anti-CD3/T cell receptor mAb. WT31 caused an increase of plasma tumor necrosis factor-alpha in all four HR patients and none of the five LR patients. In all HR patients except one, plasma gamma-interferon and interleukin 6 also increased, and a first-dose response was observed, whereas no cytokine release or adverse effects occurred in any of the LR patients. WT31 caused lymphopenia in all HR and none of the LR patients. FACS analysis demonstrated that in HR patients, after the initial disappearance of CD3+ cells from peripheral blood, modulation of CD3 occurred, whereas in LR patients a high degree of coating of the lymphocytes was observed. Surprisingly, WT31 also induced a marked granulocytopenia, as well as a decrease of thrombocytes, in three of the four HR patients (and in none of the LR patients). These data provide direct clinical evidence that Fc receptor interaction determines the release of cytokines and the occurrence of adverse effects after administration of anti-CD3/T cell receptor mAb. Furthermore, these data suggest that tumor necrosis factor-alpha by itself is not sufficient to induce the first-dose reaction.
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PMID:Role of polymorphic Fc receptor Fc gammaRIIa in cytokine release and adverse effects of murine IgG1 anti-CD3/T cell receptor antibody (WT31). 900 Jun 70

The immune system changes during the lifespan of man. Many described changes in the immune system of the elderly were dependent on illness or chronic diseases. To exclude these pathological changes in the immune system and to exclusively describe age-dependent changes, Ligthart et al. defined immunogerontological criteria to study the immune system in the elderly, the SENIEUR-Protocol. Most changes in the immune system of elderly are within the normal ranges of the appropriate parameter. However, there are many significant differences between the status of the immune system in healthy young and elderly individuals, within these normal ranges. The comparison between SENIEUR-elderly and healthy young and the additional comparison of these two groups with centenarians allows the discussion of potential pathological effects of these changes. In this article we summarize the described changes of the immune system in SENIEUR-elderly and centenarians. The serum levels of the immunoglobulins G, M and A increased with age, as well as the number of benign monoclonal gammopathies and the number of autoantibodies. The titers of zinc are significantly decreased in the serum of the elderly. The production of the acute phase protein C-reactive protein is not age-dependent, whereas the serum levels of alpha 2-macroglobulin are significantly increased in the elderly. The number of lymphocytes decreased and the number of neutrophils increased with aging. Monocytes, basophils, and eosinophils are without changes during life. There are many descriptions about changes of the leukocyte sub-population in aging, which are not always comparable. However, the number of T cells (CD3) decreases. Within the T cells the CD8 cells decreased more than the CD4 cells, resulting in an increased CD4/CD8 ratio. Memory T cells (CD45RO) increase during life, whereas naive T cells (CD45RA) decrease. Interestingly, centenarians have more naive T cells SENIEUR-elderly. The number of B cells (CD19) decreased also, whereas the number of natural killer (NK) cells (CD16, CD56, CD57) increases with aging. The capacity of leukocytes from the elderly to produce cytokines is also significantly different from those of the young. The release of the TH1-cytokines interleukin (IL)-2 and interferon (IFN)-gamma is decreased, whereas the production of the TH2-cytokines IL-4 and IL-10 is increased in the elderly. The production of proinflammatory cytokines such as IL-1, IL-6, IL-8, and tumor necrosis factor-alpha is increased in the elderly. In contrast, the capacity to produce the antiviral cytokine IFN-alpha is reduced in elderly individuals. In conclusion, the immune system shows many age-dependent changes, but we know little about the reason and the potential pathological effects of these changes.
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PMID:[Characteristics of immunologic test values in the elderly]. 933 53

Eight Japanese hemophiliacs with chronic hepatitis C (CHC) received interferon (IFN) therapy and four of them (50%) responded completely. Non-responders included 3 double-infected patients: 1 with hepatitis B virus (HBV) and 2 with human immunodeficiency virus-1 (HIV-1). In one of the patients with HIV-1 double infection, the absolute number of CD4+ lymphocytes decreased during IFN therapy. These findings suggest that hemophiliac patients with CHC can respond well to IFN therapy, but in patients who are double-infected with HBV and HIV-1, the indication of IFN therapy should be considered seriously.
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PMID:Interferon therapy for Japanese hemophiliacs with chronic hepatitis C. 936 52

The purpose of this study was to evaluate in a randomized phase II trial the efficacy and toxicity of combination biochemotherapy compared with chemotherapy alone in patients with metastatic melanoma. Sixty-five patients with metastatic melanoma (ECOG performance status 0 or 1) were randomized to receive intravenous BCNU 100 mg m(-2) (day 1, alternate courses), cisplatin 25 mg m(-2) (days 1-3), DTIC 220 mg m(-2) (days 1-3) and oral tamoxifen 40 mg (BCDT regimen) with (n = 35) or without (n = 30) subcutaneous interleukin 2 (IL-2) 18 x 10(6) iu t.d.s. (day - 2), 9 x 10(6) iu b.d. (day - 1 and 0) and interferon 2 alpha (IFN-alpha) 9 MU (days 1-3). Evidence for immune activation was determined by flow cytometric analysis of peripheral blood lymphocytes. Treatment was repeated every 4 weeks up to six courses depending on response. The overall response rate of BCDT with IL-2/IFN-alpha was 23% [95% confidence interval (CI) 10-40%] with one complete response (CR) and seven partial responses (PR), and for BCDT alone 27% (95% CI 12-46%) with eight PRs; the median durations of response were 2.8 months and 2.5 months respectively. Sites of response were similar in both groups. There was no difference between the two groups in progression-free survival or overall survival (median survival 5 months for BCDT with IL-2/IFNalpha and 5.5 months for BCDT alone). Although 3 days of subcutaneous IL-2 resulted in significant lymphopenia, evidence of immune activation was indicated by a significant rise in the percentage of CD56- (NK cells) and CD3/HLA-DR-positive (activated T cells) subsets, without any change in the percentage of CD4 or CD4 T-cell subsets. Toxicity assessment revealed a significantly higher incidence of severe thrombocytopenia in patients treated with combination chemotherapy than with chemotherapy alone (37% vs 13%, P = 0.03) and a higher incidence of grade 3/4 flu-like symptoms (20% vs 10%) and fatigue (26% vs 13%). The addition of subcutaneous IL-2 and IFNalpha to BCDT chemotherapy in a randomized phase II trial resulted in immune activation but did not improve response rates in patients with metastatic melanoma, and indeed may increase some treatment-related toxicity.
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PMID:Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen] with or without interferon alpha (IFN-alpha) and interleukin (IL-2) in patients with metastatic melanoma. 957 34


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