Immunodepressive activity of FCE 23762 on humoral and cell-mediated immune responses in normal mice: comparison with doxorubicin

Fornasiero, M. C.; Ferrari, Marisa Belicchi; Gnocchi, Paola; Trizio, D.; Isetta, Anna Maria

doi:10.1007/bf02028125

Cited by 6 publications

(5 citation statements)

References 13 publications

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“…In contrast, DOX treatment here resulted in significant reductions in IgG levels compared with those in control SEC mice. Suppressive effects of DOX on Ig formation had been reported in other studies (Fornasiero et al, 1992; Macfarlane et al, 1997). It has also been shown that DOX induces apoptosis of nonactivated and PHA-activated human peripheral blood lymphocytes and induces T- and B-lymphocyte depletion in the all major immune cell organs associated with lymphocyte growth/maturation (Ferraro et al, 2000).…”

Section: Discussionsupporting

confidence: 76%

Role of cysteinyl leukotriene receptor-1 antagonists in treatment of experimentally induced mammary tumor

2013

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It has been reported that a leukotriene (LT)-D4 receptor (i.e. cysteinyl LT1 receptor; CysLT1R) has an important role in carcinogenesis. The current study was carried out to assess the possible antitumor effects of montelukast (MON), a CysLT1R antagonist, in a mouse mammary carcinoma model, that is, a solid Ehrlich carcinoma (SEC). Effects of MON on tumor-induced immune dysfunction and the possibility that MON may modulate the antitumor and immunomodulatory effects of doxorubicin (DOX) were also studied. The effects in tumor-bearing hosts of several dosings with MON (10 mg/kg, per os), with and without the added presence of DOX (2 mg/kg, intraperitoneal), were investigated in vivo; end points evaluated included assessment of tumor volume, splenic lymphocyte profiles/functionality, tumor necrosis factor-α content, as well as apoptosis and expression of nuclear factor-κB (NF-κB) among the tumor cells. The data indicate that MON induced significant antitumor activity against the SEC. MON treatments also significantly mitigated both tumor- and DOX-induced declines in immune parameters assessed here. Moreover, MON led to decreased NF-κB nuclear expression and, in doing so, appeared to chemosensitize these tumor cells to DOX-induced apoptosis.

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Section: Discussionsupporting

confidence: 76%

Role of cysteinyl leukotriene receptor-1 antagonists in treatment of experimentally induced mammary tumor

2013

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“…7,8 Doxorubicin and related drugs also have variable effects on adaptive immune responses, with doxorubicin being immunostimulatory and preserving cell-mediated immunity in some studies. [8][9][10][11][12][13] In addition, taxane-based chemotherapeutics in humans also may be immunostimulatory. 14 In one study, alterations in immune function were documented to correlate with response to therapy.…”

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confidence: 99%

Effects of Chemotherapy on Immune Responses in Dogs with Cancer

Walter

Biller

Lana

et al. 2006

Veterinary Internal Medicne

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Chemotherapy is assumed to be immunosuppressive; yet to the authors' knowledge, the effects of common chemotherapy protocols on adaptive immune responses in dogs with cancer have not been fully evaluated. Therefore, a study was conducted to evaluate the effects of 2 common chemotherapy protocols on T- and B-cell numbers and humoral immune responses to de novo vaccination in dogs with cancer. Twenty-one dogs with cancer (12 with lymphoma, 9 with osteosarcoma) were enrolled in a prospective study to assess effects of doxorubicin versus multi-drug chemotherapy on adaptive immunity. Numbers of circulating T and B cells were assessed by flow cytometry, and antibody responses to de novo vaccination were assessed before, during, and after chemotherapy. The T- and B-cell numbers before treatment also were compared with those of healthy, age-matched, control dogs. Prior to treatment, dogs with cancer had significantly fewer (P < .05) CD4+ T cells and CD8+ T cells than did healthy dogs. Doxorubicin treatment did not cause a significant decrease in T- or B-cell numbers, whereas treatment with combination chemotherapy caused a significant and persistent decrease in B-cell numbers. Antibody titers after vaccination were not significantly different between control and chemotherapy-treated dogs. These findings suggest that chemotherapy may have less impact on T-cell numbers and ability to mount antibody responses in dogs with cancer than was previously anticipated, though dogs with lymphoma or osteosarcoma appear to be relatively T-cell deficient before initiation of chemotherapy.

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“…The decrease in the amount of the splenocytes is of interest, since it is well known that streptomycetes are producers of anthracyclines, such as daunorubicin and doxorubicin, drugs widely used in cancer chemotherapy (2). Their deleterious effects on splenocytes have been demonstrated in several studies (8,9,46). These agents have been shown to cause a rapid and massive depletion of T and B lymphocytes, especially in the spleen, moderate levels of depletion in the lymph nodes, and lower levels of depletion in the thymus after injection of a single low intraperitoneal dose in the mouse (8).…”

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confidence: 99%

Systemic Immunoresponses in Mice after Repeated Exposure of Lungs to Spores of Streptomyces californicus

Jussila

Pelkonen

Kosma

et al. 2003

Clin Vaccine Immunol

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Microbial growth in moisture-damaged buildings is associated with respiratory and other symptoms in the occupants. Streptomyces spp. are frequently isolated from such buildings. In the present study, we evaluated the responses of mice after repeated exposure to spores of Streptomyces californicus. Mice were exposed via intratracheal instillation to six doses (at 7-day intervals) of the spores of S. californicus, originally isolated from the indoor air of a moisture-damaged building, at three dose levels (2 ؋ 10 3 , 2 ؋ 10 5 , and 2 ؋ 10 7 spores). Inflammation and toxicity, including changes in cell populations in the lungs, lymph nodes, and spleen, were evaluated 24 h after the last dosage. The exposure provoked a dose-dependent inflammatory cell response, as detected by the intense recruitment of neutrophils, but the numbers of macrophages and lymphocytes in the airways also increased. The cellular responses corresponded to the dose-dependent increases in inflammationand cytotoxicity-associated biochemical markers (i.e., levels of albumin, total protein, and lactate dehydrogenase) in bronchoalveolar lavage fluid. The spore exposure increased the number of both activated and nonactivated T lymphocytes. Also, the amounts of CD3 ؊ CD4 ؊ and unconventional CD3 ؊ CD4 ؉ lymphocytes in the lung tissue were augmented. Interestingly, the spore exposure decreased cells in the spleen. This effect was strongest at the dose of 2 ؋ 10 5 spores. These results indicate that the spores of S. californicus are capable of provoking both immunostimulation in lungs (inflammation) and systemic immunotoxicity, especially in the spleen. The immunotoxic effect resembled that caused by chemotherapeutic agents, originally isolated from Streptomyces spp. Thus, S. californicus must be considered a microbial species with potential to cause systemic adverse health effects in occupants of moisture-damaged buildings.Microbial growth subsequent to moisture damage in buildings has been connected to increased adverse respiratory and other harmful health effects (7,32,33,37,38,44). Increased numbers of microbial spores are present in the indoor air of moisture-damaged buildings (15,16,27). Moreover, several of the microbial species that are frequently detected in moisturedamaged buildings are rarely observed in reference buildings (34). The spores are inhaled deeply into the lungs due to their relatively small particle size (23). Since the spores may also deliver nonvolatile microbial toxins into the lungs (36), they presumably play a role in provoking adverse health effects.Streptomyces californicus is a sporulating gram-positive bacterium that is used as a moisture indicator and that is frequently isolated from the indoor air of moisture-damaged buildings (27,34). Streptomycetes have the genetic capability to produce many bioactive secondary metabolites, such as antibiotics, immunosuppressive agents, antitumor substances, and inhibitors of Ca 2ϩ -and calmodulin-dependent cyclic nucleotide phosphodiesterases, which are important enzymes involved ...

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Immunodepressive activity of FCE 23762 on humoral and cell-mediated immune responses in normal mice: comparison with doxorubicin

Cited by 6 publications

References 13 publications

Role of cysteinyl leukotriene receptor-1 antagonists in treatment of experimentally induced mammary tumor

Role of cysteinyl leukotriene receptor-1 antagonists in treatment of experimentally induced mammary tumor

Effects of Chemotherapy on Immune Responses in Dogs with Cancer

Systemic Immunoresponses in Mice after Repeated Exposure of Lungs to Spores of Streptomyces californicus

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