Thalidomide Stimulates Splenic IgM Antibody Response and Cytotoxic T Lymphocyte Activity and Alters Leukocyte Subpopulation Numbers in Female B6C3F1 Mice

Karrow, Niel A.; McCay, J. A.; Brown, R. D.; Musgrove, D. L.; Pettit, Denise; Munson, Albert E.; Germolec, Dori R.; White, Kimber L.

doi:10.1006/taap.2000.8939

Cited by 22 publications

(6 citation statements)

References 30 publications

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“…For intraperitoneal injection, thalidomide was dissolved in DMSO (Aldrich Chemical, Milwaukee, WI, USA), and administered in a 0.1 ml volume for intraperitoneal bolus injection of thalidomide to deliver 0 (DMSO alone, vehicle control), 100 or 400 mg/kg of this pharmacologic agent 1 h before UVB exposure. This dosing regimen has been demonstrated to mimic steady‐state serum levels as achieved by standard oral dosing regimens (24, 25) For in vitro media addition, thalidomide was dissolved in DMSO prior to media addition with a final concentration of 132 μM in 1% DMSO. For the in vitro dose–response study, the concentrations used were 132, 44, 4.5 and 0.5 μM, all in 1% DMSO in complete RPMI.…”

Section: Methodsmentioning

confidence: 99%

Thalidomide inhibits UVB‐induced mouse keratinocyte apoptosis by both TNF‐α‐dependent and TNF‐α‐independent pathways

Brenneman

Burns

et al. 2003

Photoderm Photoimm Photomed

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Thalidomide has been shown to selectively inhibit TNF-α production in vitro by lipopolysaccharide (LPS)-stimulated monocytes. TNF-α has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-α and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-α, IL-6, IL-10, IL-1ß, GM-CSF and IFN-γ were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-α levels were reduced by 93%, in a dose-dependent manner, and TNF-α mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a twofold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-γ. The LD 50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death. Correspondence A.L. Moreira

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Section: Methodsmentioning

confidence: 99%

Thalidomide inhibits UVB‐induced mouse keratinocyte apoptosis by both TNF‐α‐dependent and TNF‐α‐independent pathways

Brenneman

Burns

et al. 2003

Photoderm Photoimm Photomed

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“…For instance, in patients with HIV infection, an increase in CD8 + T cells and IL-12 levels were observed during treatment with thalidomide [13]. Similarly, Karrow et al [21] could demonstrate that in female B6C3F1 mice thalidomide stimulates cytotoxic T-cell responses and leads to an increase in the absolute numbers of CD8 + T cells. During thalidomide treatment of SIV-infected cynomolgus monkeys, thalidomide's ability to inhibit TNF-a production was associated with an increased expression of CD28 cell surface receptors on CD4 + T cells with a decrease on CD8 + T cells [22].…”

Section: Introductionmentioning

confidence: 94%

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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“…Another approach for therapeutic stimulation of the immune response is to use small molecule drugs to precisely modulate key events (Davies et al, 2001;Kumar et al, 2004). In the case of thalidomide, beneficial immunomodulatory effects may have been discovered inadvertently in studies designed to determine immunosuppressive activity (Karrow et al, 2000). Research into these various therapeutic modalities is making great advances.…”

Section: Immunostimulationmentioning

confidence: 99%

Multidimensional Immunomodulation

House¹,

Hastings²

2004

Journal of Immunotoxicology

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Thalidomide Stimulates Splenic IgM Antibody Response and Cytotoxic T Lymphocyte Activity and Alters Leukocyte Subpopulation Numbers in Female B6C3F1 Mice

Cited by 22 publications

References 30 publications

Thalidomide inhibits UVB‐induced mouse keratinocyte apoptosis by both TNF‐α‐dependent and TNF‐α‐independent pathways

Thalidomide inhibits UVB‐induced mouse keratinocyte apoptosis by both TNF‐α‐dependent and TNF‐α‐independent pathways

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

Multidimensional Immunomodulation

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