Thalidomide Inhibits Granulocyte Responses in Healthy Humans after Ex Vivo Stimulation with Bacterial Antigens

Juffermans, Nicole P.; Verbon, Annelies; Schultz, Marc J.; Hack, C. E.; Deventer, S. J. H. Van; Speelman, Peter; Poll, Tom van der

doi:10.1128/aac.45.5.1547-1549.2001

Cited by 13 publications

(7 citation statements)

References 15 publications

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“…CD11b, CD62L and CD162). Our observations with respect to CD11b and CD62L are consistent with an earlier report showing that thalidomide treatment did not modify the expression of these molecules on neutrophils [33], but not with other studies, which noted that these molecules were down-regulated by thalidomide [34,35]. The fall in neutrophil numbers was not related to the relatively minor increases in platelet binding and neutrophil apoptosis.…”

Section: Discussionsupporting

confidence: 94%

The neutropenia induced by the thalidomide analogue CC-4047 in patients with multiple myeloma is associated with an increased percentage of neutrophils bearing CD64

McCarthy¹,

Macey²,

Streetly³

et al. 2006

International Immunopharmacology

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Section: Discussionsupporting

confidence: 94%

The neutropenia induced by the thalidomide analogue CC-4047 in patients with multiple myeloma is associated with an increased percentage of neutrophils bearing CD64

McCarthy¹,

Macey²,

Streetly³

et al. 2006

International Immunopharmacology

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“…27,28 Recently, these cells have also been implicated in the pathogenesis of CHF, possibly related to their ability to stimulate an inappropriate production of nitric oxide. 29 Previous reports have shown that thalidomide attenuates neutrophil activation, 30 and one might hypothesize that the downregulatory effect of thalidomide on neutrophils contributes to its beneficial effects in CHF.…”

Section: Discussionmentioning

confidence: 99%

Effect of Thalidomide on Cardiac Remodeling in Chronic Heart Failure

Gullestad¹,

Ueland²,

Fjeld³

et al. 2005

Circulation

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Background-Inflammation and matrix degradation may play a pathogenic role in chronic heart failure (CHF), and therefore, we examined whether thalidomide, a drug with potential immunomodulating and matrix-stabilizing properties, could improve left ventricular (LV) function in patients with CHF secondary to idiopathic dilated cardiomyopathy (IDCM) or coronary artery disease (CAD). Methods and Results-Fifty-six patients with CHF and an LV ejection fraction (LVEF) Ͻ40% who were already on optimal conventional cardiovascular treatment were randomized to thalidomide (25 mg QD increasing to 200 mg QD) or placebo and followed up for 12 weeks. Our main findings were as follows: (1) During thalidomide treatment but not during placebo, there was a marked increase in LVEF (Ϸ7 EF units) along with a significant decrease in LV end-diastolic volume and heart rate. (2) This improvement in LVEF was accompanied by a decrease in matrix metalloproteinase-2 without any changes in its endogenous tissue inhibitor, suggesting a matrix-stabilizing net effect.(3) Thalidomide also induced a decrease in total neutrophil count and an increase in plasma levels of tumor necrosis factor-␣, suggesting both proinflammatory and antiinflammatory effects. (4) The effect of thalidomide on LVEF was more marked in IDCM than in CAD, possibly partly reflecting that the former group was able to tolerate a higher thalidomide dosage. Conclusions-Although our results must be confirmed in larger studies that also examine the effects on morbidity and mortality, our findings suggest a role for thalidomide in the management of CHF in addition to traditional cardiovascular medications. (Circulation. 2005;112:3408-3414.)

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“…From our literature review it would appear that this is the first report of meningitis developing under thalidomide treatment. Development of bacterial meningitis at the beginning of thalidomide treatment, on the fourth and sixth day in our cases, is not a chance occurrence; in a small-sized experimental study, Juffermans et al 8 demonstrated that the effect of thalidomide on deterioration of neutrophil functions becomes evident after 3 hours and lasts at least 24 hours.…”

Section: Discussionmentioning

confidence: 44%

“…Thalidomide attenuated neutrophil chemotaxis in vitro but did not influence respiratory burst activity. 8 The blood-brain barrier (BBB) endothelium expresses multiple leukocyte adhesion molecules and presents chemotactic factors such as interleukin-8 when activated by inflam-matory mediators such as TNF-a, nitric oxide, and matrix metalloproteinase-2. This combination promotes neutrophil adherence and transendothelial migration.…”

Section: Discussionmentioning

confidence: 99%

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Two cases of bacterial meningitis accompanied by thalidomide therapy in patients with multiple myeloma: is thalidomide associated with bacterial meningitis?

Paşa

Altıntaş

Çil

et al. 2009

International Journal of Infectious Diseases

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Morbidity and mortality in multiple myeloma is often attributed to life-threatening infections. A defect in humoral immunity has been proposed for the predisposition to bacterial infections. Most of the infections are of bacterial origin, and the most serious are septicemia, meningitis, and pneumonia. Thalidomide is a drug with pleiotropic effects. The immunomodulatory effects of thalidomide are at least partially mediated through its ability to down-regulate the pathogenic over-production of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a cytokine that plays a central role in the regulation of the host immune and inflammatory response to infection. In the central nervous system, TNF-alpha is involved in induction of a fever response and triggers the release of other cytokines, and may also influence transport of compounds into the brain, leading to cerebrospinal fluid leukocytosis, increased protein influx, and lactate accumulation. Thalidomide has been shown to down-regulate the production of TNF-alpha. On the other hand, knowledge of the effects of thalidomide on granulocyte functions is limited. Thalidomide has been shown to attenuate neutrophil adhesion and chemotaxis. We present herein two cases of Streptococcus pneumoniae bacterial meningitis that developed soon after the initiation of thalidomide treatment, and discuss the effect of thalidomide on the immune system. Although, it is not clear whether thalidomide caused the development of the bacterial infections and meningitis, or what its pathogenetic mechanisms are, physicians should be alert for signs and symptoms of meningitis in patients with multiple myeloma who are treated with thalidomide, especially those in neutropenic states.

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Thalidomide Inhibits Granulocyte Responses in Healthy Humans after Ex Vivo Stimulation with Bacterial Antigens

Cited by 13 publications

References 15 publications

The neutropenia induced by the thalidomide analogue CC-4047 in patients with multiple myeloma is associated with an increased percentage of neutrophils bearing CD64

The neutropenia induced by the thalidomide analogue CC-4047 in patients with multiple myeloma is associated with an increased percentage of neutrophils bearing CD64

Effect of Thalidomide on Cardiac Remodeling in Chronic Heart Failure

Two cases of bacterial meningitis accompanied by thalidomide therapy in patients with multiple myeloma: is thalidomide associated with bacterial meningitis?

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