The kinetics of circulating cytokines including IL-6, TNF-α, IL-8 and IL-10 following allogeneic hematopoietic stem cell transplantation

Min, Chang‐Ki; Lee, W Y; Min, Do June; Lee, D G; Kim, Y J; Park, Y H; Kim, H J; Lee, Sae-Mi; Kim, D W; Lee, Jung Woo; Min, Woo Sung; Kim, C C

doi:10.1038/sj.bmt.1703258

Cited by 87 publications

(60 citation statements)

References 16 publications

(13 reference statements)

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“…22,23 In BMT setting, IL-6 is known to be the most important cytokine during the initial inflammatory response and correlates significantly with the TNF-a level. 24 Therefore, the development of an osteoclast lineage following a BMT may be supported by these bone-resorbing cytokines.…”

Section: Discussionmentioning

confidence: 99%

Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation

Lee

Baek

Rhee

et al. 2004

Bone Marrow Transplant

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Summary:Cytokines including IL-6 and TNF-a play an important role in the pathogenesis of postmenopausal osteoporosis. However, the relationship between changes in the cytokine levels and subsequent bone loss in patients undergoing a bone marrow transplantation (BMT) is unclear. A total of 46 patients undergoing an allogeneic BMT were prospectively investigated. The bone turnover markers and the serum cytokines were measured before BMT and serially after BMT. Bone mineral density (BMD) was measured before and 1 year after BMT. At 1 year after BMT, the lumbar spine BMD had decreased by 4.8%, and the total proximal femoral BMD had decreased by 12.3%. The serum IL-6 and TNF-a levels increased until 2 and 3 weeks after BMT, respectively. The lumbar BMD was significantly decreased as the serum IL-6 and TNF-a levels increased by post-BMT 3 weeks. The lumbar BMD decreased significantly as the cumulative prednisolone and cyclosporine dose increased. Patients with GVHD Xgrade II had higher lumbar bone loss than patients with GVHD ograde I. In conclusion, immunosuppressants, GVHD occurrence and increase in bone-resorbing cytokines in the early post-BMT period were associated with later bone loss after BMT. Further studies are needed to elucidate the precise mechanism. Bone marrow transplantation (BMT) is an established method for treating various hematological diseases. As the number of long-term survivors increased due to the improved prognosis after BMT, the number of endocrine complications has also increased. Endocrine complications brought about after a BMT include hypogonadism, thyroid dysfunction, hypopituitarism, diabetes and osteoporosis. A significant bone loss occurs during the first year after a BMT with up to a 5-10% decrease in the bone mineral density (BMD) in the lumbar spine and proximal femur. The post-BMT bone loss is mainly related to the immunosuppressants and the gonadal dysfunctions secondary to myeloablative therapy and/or total body irradiation (TBI). [1][2][3][4][5] The rapid impairment in bone formation and the increase in bone resorption, as mirrored by the biochemical markers, might play a role in bone loss, particularly during the early post-BMT period. 1 The pathogenic role of the cytokines is well known in the development of postmenopausal osteoporosis and other forms of secondary osteoporosis. Interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a) are known to increase bone resorption by stimulating osteoclasts. 6 However, there are few reports on the relationship between changes in the bone metabolism and cytokine levels after a BMT. 7,8 In particular, there is no report on the effects of the drastically changing cytokine levels in the early post-BMT period on the long-term changes in the BMD after a BMT. It was previously reported that the bone marrow plasma IL-6 level, which reflects the real changes in the bone marrow microenvironment, was significantly related to the serum bone resorption markers after a BMT. 8 This study measured the serum IL-6, TNF-a and bone ...

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Section: Discussionmentioning

confidence: 99%

Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation

Lee

Baek

Rhee

et al. 2004

Bone Marrow Transplant

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“…[24][25][26][27][28][29][30][31][32][33][34][35] The wide discrepancies may be attributable to the diversity of the diseases transplanted, the transplant conditioning (notably inclusion of antithymocyte globulin); 23 genetic diversity, including cytokine (receptor) gene polymorphisms, [36][37][38][39][40] infection, veno-occlusive disease and lymphocytopenia in the case of transient IL-7 and IL-15 increases. [3][4][5][6]29,41,42 However, the achievement of full lymphoid chimerism has so far not been identified as a significant moment for cytokine changes.…”

Section: Discussionmentioning

confidence: 99%

Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation

Melenhorst

Tian

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundAllogeneic hematopoietic stem cell transplantation is associated with profound changes in levels of various cytokines. Emphasis has been placed on conditioning-associated mucosal damage and neutropenia and associated bacterial translocation as the initiating conditions predisposing to acute graft-versus-host disease. The post-transplant period is, however, also associated with increases in certain homeostatic cytokines. It is unclear how much the homeostatic drive to lymphocyte recovery and the production of cytokines from the engrafting donor immune system determine cytokine fluctuations in the peri-and immediate post-transplant period. The aim of this study was to examine the contributions of the conditioning regimen, donor engraftment, infections, and graft-versus-host disease to fluctuations in cytokines involved in homeostasis and inflammation. Design and MethodsWe examined the levels of 33 cytokines in relation to peri-and post-transplant events such as conditioning regimen, chimerism, and acute graft-versus-host disease in myeloablative, non-T cell-replete HLA-identical sibling donor stem cell transplantation for hematologic malignancies. ResultsWe identified two cytokine storms. The first occurred following conditioning and reached peak levels when all the leukocytes were at their lowest concentrations. The second cytokine storm occurred concurrently with hematopoietic reconstitution and subsided with the achievement of full donor lymphocyte chimerism. ConclusionsOur results indicate that both recipient-related and donor-related factors contribute to the changes in cytokine levels in the recipient following allogeneic hematopoietic stem cell transplantation. The study reported here was performed using plasma samples drawn from patients enrolled in the ClinicalTrials.gov-registered trials NCT00467961 and NCT00378534

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“…GVHD, infection, and conditioning for HSCT can be associated with increases in serum levels of inflammatory cytokines, [31][32][33][34] whose altered levels might influence NK function and licensing. [35][36][37] To investigate whether the alteration of NK response in the early stage after HSCT was associated with increased plasma cytokine levels in the patient, we measured the levels of TNF-␣, IFN-␥, IL-2, IL-15, IL-6, and IL-12 by ELISA assay at multiple time points after HSCT.…”

Section: Posttransplantation Plasma Cytokine Levels Are Not Associatementioning

confidence: 99%

Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell–depleted allogeneic hematopoietic cell transplantation

Venstrom²,

Liu

et al. 2009

Blood

114

124

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The kinetics of circulating cytokines including IL-6, TNF-α, IL-8 and IL-10 following allogeneic hematopoietic stem cell transplantation

Cited by 87 publications

References 16 publications

Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation

Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation

Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation

Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell–depleted allogeneic hematopoietic cell transplantation

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