Effect of cytokine modulation by thalidomide on the granulomatous response in murine tuberculosis

Moreira, André L.; Tsenova-Berkova, L; Wang, J.; Laochumroonvorapong, Pairote; Freeman, Sherry; Freedman, Victoria H.; Kaplan, Gilla

doi:10.1016/s0962-8479(97)90015-0

Cited by 73 publications

(39 citation statements)

References 27 publications

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“…3 Thalidomide inhibits the upregulation of IL-6 and downregulates nuclear factor-kB activity, both of which are elevated and important in the CNS inflammatory process seen in neurosarcoidosis. 4,5 In our patient, we cannot rule out that the improvement noted clinically and radiologically after initiation of thalidomide was simple natural course of disease, which includes spontaneous remissions and relapses, or a delayed response to steroids. However, the failure to respond clinically and radiologically to i.v.…”

Section: Discussionmentioning

confidence: 77%

Thalidomide for acute treatment of neurosarcoidosis

2007

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Section: Discussionmentioning

confidence: 77%

Thalidomide for acute treatment of neurosarcoidosis

2007

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“…In addition, thalidomide may have mitigated some IFN related side effects probably by suppressing IFN mediated cytokine expression as previously shown in murine granulomatous tissue 24 or isolated human macrophages, 25 enabling patients to stay longer on maintenance treatment. Survival after discontinuation of maintenance therapy was remarkably long and did not differ significantly between the maintenance groups ( Figure 3B).…”

Section: Discussionmentioning

confidence: 87%

Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma

Ludwig¹,

Adam²,

Tóthová³

et al. 2010

Haematologica

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BackgroundThalidomide maintenance therapy after stem cell transplantation resulted in increased progression-free survival and overall survival in a few trials, but its role in non-transplant eligible patients with multiple myeloma remains unclear. This study assessed the impact of thalidomide-interferon in comparison to interferon maintenance therapy in elderly patients with multiple myeloma. Design and MethodsOf 289 elderly patients with multiple myeloma who were randomized to thalidomide-dexamethasone or melphalan-prednisolone induction therapy, 137 finally completed 9 cycles of induction therapy with stable disease or better and thereby qualified for maintenance treatment. Of these, 128 have been randomized to either thalidomide-interferon or interferon alone. Primary study endpoints were progression-free survival and response rates; secondary endpoints were overall survival, toxicity and quality of life. ResultsThalidomide-interferon maintenance therapy led to a significantly longer progression-free survival compared to interferon (27.7 vs. 13.2 months, P=0.0068), but overall survival was similar in both groups (52.6 vs. 51.4 months, P=0.81) and did not differ between patients aged 75 years or older, or younger patients (P=0.39). Survival after disease progression tended to be shorter in patients on thalidomide-interferon maintenance therapy (P=0.056). Progression-free survival and overall survival tended to be shorter in patients with adverse cytogenetic (FISH) findings compared to the standard risk group but differences were not significant (P=0.084 and P=0.082, respectively). Patients on thalidomide-interferon presented with more neuropathy (P=0.0015), constipation (P=0.0004), skin toxicity (P=0.0041) and elevated creatinine (P=0.026). ConclusionsThalidomide plus interferon maintenance therapy increased progression-free survival but not overall survival and was associated with slightly more toxicity than maintenance with interferon alone. (ClinicalTrials.gov Identifier: NCT00205751).Key words: thalidomide, thalidomide-interferon, progression-free survival, overall survival. Haematologica 2010;95(9):1548-1554. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Ludwig H, Adam Z, Tóthová E, Hajek R, Labar B, Egyed M, Spicka I, Gisslinger H, Drach J, Kuhn I, Hinke A, and Zojer N.Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma.Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma

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“…2A, 2B). Kaplan et al [29] have shown that production of the proinflammatory cytokines tumour necrosis factor-␣ (TNF-␣) interleukin-6 (IL-6) and IFN-␥ was positively associated with the CFU counts and extensive tissue damage in the lungs of M. tuberculosis-infected mice. The accumulation of IFN-␥ might elicit the secretion of a higher level of proinflammatory cytokines [30] and platelet-derived growth factors [31], resulting in a chronic inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Diversity of Lung and Spleen Immune Responses in Mice with Slowly Progressive Primary Tuberculosis

et al. 2000

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The aim of the present study was to assess the compartmentalized immune response, in terms of cytokine secretion and cell activation, in lungs and spleens of mice with slowly progressive primary tuberculosis. Immunocyte populations from both organs were isolated and stimulated with concanavalin A, purified protein derivatives and MPT 59. Production of interferon-␥ (IFN-␥) and interleukin-4 (IL-4) was measured using an enzyme-linked immunosorbent assay, and cell activation was measured using a tetrazolium colorimetric assay. The IFN-␥ and IL-4 levels in the supernatants of Mycobacterium tuberculosis antigen (Ag)-stimulated lung immunocytes from infected mice were higher than the levels from uninfected mice. However, only IL-4 levels were raised in the supernatants of Ag-stimulated spleen immunocytes from infected mice. Spontaneous and Ag-stimulated immunocyte activation was lower only in the lungs of infected mice compared with uninfected mice. The level of lung immunocyte activation was inversely associated with the extent of gross pulmonary pathology. In conclusion, cytokine secretion and cell activation were different between lungs and spleens in slowly progressive primary murine tuberculosis. Cytokine diversity may explain the confinement of tuberculous lesions in the lungs and the absence of lesions in the spleens of mice with slowly progressive tuberculosis.

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Effect of cytokine modulation by thalidomide on the granulomatous response in murine tuberculosis

Cited by 73 publications

References 27 publications

Thalidomide for acute treatment of neurosarcoidosis

Thalidomide for acute treatment of neurosarcoidosis

Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma

Diversity of Lung and Spleen Immune Responses in Mice with Slowly Progressive Primary Tuberculosis

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