Thalidomide and Its Metabolites Have No Effect on Human Lymphocyte Proliferation

Santos‐Mendoza, Teresa; Favila-Castillo, L; Oltra, A; Tamariz, Joaquı́n; Labarrios, Fernando; Estrada‐Parra, Sergio; Estrada-Garcı́a, Iris

doi:10.1159/000237338

Cited by 13 publications

(7 citation statements)

References 8 publications

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“…Santos-Mendoza et al [26] studied the in vivo and in vitro effects of thalidomide on lymphocyte proliferation in normal humans in response to mycobacterial antigens and a mitogen, but neither thalidomide nor its metabolites affected the lymphoproliferative response of human T lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

The ratio between CD4 + and CD8 + cells in the peripheral blood of patients with hematological malignancies is not altered by thalidomide

Strupp¹,

Germing²,

Aivado³

et al. 2005

Leukemia & Lymphoma

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Thalidomide is thought to have anti-angiogenic and immunomodulatory properties, including suppression of tumor necrosis factor-alpha, effects on interleukins and interferons, down-regulation of some cell adhesion molecules, and changes in the proportion of lymphocyte subsets. It is unclear whether the clinical response to thalidomide in patients with multiple myeloma (MM), idiopathic myelofibrosis (IM), and myelodysplastic syndromes (MDS) is related to its ability to inhibit angiogenesis or its immunomodulatory effects. We examined the effect of thalidomide on T-lymphocyte subsets in 18 patients with MDS, 6 patients with MM, 4 patients with IM, and 3 patients with angioimmunoblastic lymphoma (AILD). These patients had either a relapse or progressive disease following cytotoxic chemotherapy including high-dose chemotherapy with autologous stem cell support. Thalidomide was first administered at 100 mg/day p.o. and increased to 400 mg/day. T-lymphocyte subsets (CD4+, CD8+) were measured by fluorescence-activated cell sorter (FACS) before and during treatment with thalidomide. Twenty-six of 31 patients responded to thalidomide, most of them achieving partial remission. The median concentration of CD4+ cells was 443/microl, the median of CD8+ cells was 359/microl (CD3 992/microl). In our cohort, no significant changes in absolute numbers or proportions of CD3+ (P = 0.12), CD4+ (P = 0.668), or CD8+ (P = 0.143) cells were observed following the treatment with thalidomide. Although the CD4/CD8 ratio declined from 1.6 to 1.0 during 3 months of thalidomide treatment, this had no statistical significance (P = 0.1). Our findings show that an effect of thalidomide on the T lymphocytes studied is unlikely to be of major importance for the clinical effects.

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Section: Discussionmentioning

confidence: 99%

The ratio between CD4 + and CD8 + cells in the peripheral blood of patients with hematological malignancies is not altered by thalidomide

Strupp¹,

Germing²,

Aivado³

et al. 2005

Leukemia & Lymphoma

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“…In vitro studies with retinal pigment epithelium have shown inhibition of cell migration and cell proliferation (Spraul et al . 1999), whereas no effect has been observed in human lymphocytes (Santos‐Mendoza et al . 1996).…”

Section: Discussionmentioning

confidence: 99%

“…Other possible effects, as mutagenic and antiproliferative agents, remain controversial (Hatfill et al . 1991; Kida 1994; Santos‐Mendoza et al . 1996).…”

Section: Introductionmentioning

confidence: 99%

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Antiproliferative effect of thalidomide alone and combined with carmustine against C6 rat glioma

Arrieta

Guevara

Tamariz

et al. 2002

Int J Experimental Path

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Summary. Thalidomide could have therapeutic applications in neoplasms and in other diseases, particularly those of autoimmune origin. The objective of this study was to investigate the effect of various doses of thalidomide on the growth of C6 glioma in rats, and to determine its effects on parameters of cell proliferation and angiogenesis. Additionally, we investigated a potential enhancement of the antitumoral action of thalidomide when combined with a low dose of the antineoplastic carmustine. C6 glioma cells were implanted subcutaneously in Wistar rats. A highly malignant glioma developed in 80% of animals. When the tumour reached 2.0 cm diameter thalidomide was administered at doses of 100, 200 or 400 mg/kg/day. When given at a dose of 400 mg/kg/day thalidomide significantly reduced the tumour volume, the mitotic index and cell proliferation but not the vascular density. The combination of thalidomide plus carmustine increased the inhibitory effect on tumoral growth. Our results indicate that thalidomide is effective against malignant glioma; apparently by an antiproliferative effect, rather than by inhibition of angiogenesis; when combined with carmustine it could increase the response of glioma to antineoplastic treatment.

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“…A novel potential mechanism to explain the teratogenicity of thalidomide could be through down‐regulation of adhesion receptors on embryonic cells (16). Other possible effects, as mutagenic (17) and antiproliferative agent (3) remain controversial (18,19).…”

Section: Discussionmentioning

confidence: 99%

Effect of thalidomide in different tumors in rodents

et al. 2002

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This study investigated the effects of chronic administration of thalidomide on three different neoplasms of ectodermic origin in rodents: 1) chemically induced tumors of the nervous system of rats by transplacental exposure to ethylnitrosourea; 2) transplanted RPMI-1846 melanoma in hamsters and 3) transplanted C6 glioblastoma in rats. No effects were seen on thalidomide-treated rats on the frequency- and time of tumor development induced by ethylnitrosourea. In contrast, a reduction in tumoral growth and mitotic-index was obtained in animals treated with thalidomide in transplanted tumors, melanoma and glioblastoma, when compared with controls (P < 0.001 and 0.025, respectively). These results suggest that, although thalidomide is not a cytotoxic drug for neoplastic cells, it might partially inhibit the tumoral growth through any of its pharmacological actions; by blockage of cell-surface adhesion receptors induction of DNA oxidation, or inhibition of angiogenesis. Further investigations on the use of thalidomide perhaps associated to cytotoxic drugs, for treatment of ectodermic neoplasms seem guaranteed.

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Thalidomide and Its Metabolites Have No Effect on Human Lymphocyte Proliferation

Cited by 13 publications

References 8 publications

The ratio between CD4 + and CD8 + cells in the peripheral blood of patients with hematological malignancies is not altered by thalidomide

The ratio between CD4 + and CD8 + cells in the peripheral blood of patients with hematological malignancies is not altered by thalidomide

Antiproliferative effect of thalidomide alone and combined with carmustine against C6 rat glioma

Effect of thalidomide in different tumors in rodents

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