A study of cytokine production in acute graft-vs-host disease

Smith, Sidney R.; Terminelli, Carol; Kenworthy-Bott, Lynne; Phillips, David L.

doi:10.1016/0008-8749(91)90307-w

Cited by 34 publications

(11 citation statements)

References 16 publications

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“…Cytokines have been investigated by several groups using both RT-PCR and protein assay analyses (5,6,8,42). All of these studies point to the early (day 8 -10 peak) production of IFN-␥, in both spontaneous and stimulated (anti-CD3 or T cell mitogen) cell cultures.…”

Section: Discussionmentioning

confidence: 99%

Early Intestinal Th1 Inflammation and Mucosal T Cell Recruitment During Acute Graft-Versus-Host Reaction

Snider

Liang

2001

The Journal of Immunology

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Little is understood about the earliest cytokine responses and the role(s) of donor CD4 T cells in the intestine during the induced graft-vs-host reaction (GVHR). We investigated the activation and mucosal homing phenotype of the donor CD4 cells and the kinetics of cytokine responses within the intestine and associated lymphoid tissues during early GVHR. Significant frequencies of donor CD4 cells accumulated within recipient Peyer’s patches (PP), mesenteric lymph nodes (MLN), lamina propria (LP), and spleen (SP), during the first 9 days of GVHR. Many donor CD4 cells in SP, MLN, and LP expressed CD44 and also expressed de novo the mucosal homing integrin α4β7 (LPAM-1). A large IFN-γ response occurred by day 3 in cells from PP and MLN, but much later (day 9) in SP and LP cells. IL-10 production by SP and MLN cells was elevated initially but declined substantially by day 9. IL-4 production by SP, MLN, and PP cells was low on day 3 and showed gradual decline in LP by day 9. IL-5 production by LP cells gradually increased in direct contrast to IL-5 production by MLN cells. The MLN CD4 cells showed the most dynamic changes, with high numbers of activated/effector donor CD4 cells and altered cytokine production consistent with a developing Th1 response. The IFN-γ responses in PP and MLN preceded that of the SP, suggesting an intestinal origin for some Th1 effector cells in GVHR. Donor CD4 T cells apparently acquire the ability to home to the LP during early GVHR.

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Section: Discussionmentioning

confidence: 99%

Early Intestinal Th1 Inflammation and Mucosal T Cell Recruitment During Acute Graft-Versus-Host Reaction

Snider

Liang

2001

The Journal of Immunology

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“…CsA has recently been shown to alter functional responses in a variety of other immune cells. Treatment with CsA inhibits interleukin-1 (IL-1) and tumor necrosis factor (TNF) production [2], HLA-DR expression [3], tumoricidal activity [4] and superoxide production [5] by cells of myeloid lineage. In basophils and mast cells, CsA inhibits degranulation in response to IgE.…”

Section: Introductionmentioning

confidence: 99%

Differential anti-inflammatory effects of immunosuppressive drugs: Cyclosporin, rapamycin and FK-506 on inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and PGE2 production

et al. 2000

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These studies characterize differential mechanistic capacity of the immunophilin-binding immunosuppressive drugs (comparable to hydrocortisone) to inhibit both iNOS and COX-2 expression. Inhibition of iNOS and COX-2 mRNA accumulation by cyclosporin and rapamycin seem to be distinct. These studies also highlight potential anti-inflammatory properties of these drugs in addition to their known immunosuppressive activity.

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“…The cytokines that have been previously implicated include TNF-␣, IL-1, IL-12, IFN-␥. [1][2][3][4][5][6][7][8][9][10][11][12] Finally, cytokines and their inhibitors affect the polarization of T cells. Th1 cells that produce IL-2 and IFN-␥ tend to be associated with GVHD, while Th2 cell predominance tends to diminish the risk of GVHD.…”

mentioning

confidence: 99%

A phase I/II double-blind, placebo-controlled study of recombinant human interleukin-11 for mucositis and acute GVHD prevention in allogeneic stem cell transplantation

Antin

Lee

Neuberg

et al. 2002

Bone Marrow Transplant

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Summary:Interleukin-11 (IL-11) decreases cytokine release and increases survival in murine BMT models. In these systems, it reduces gut permeability, partially polarizes T cells to a Th2 phenotype, down-regulates IL-12, prevents mucositis, and accelerates recovery of oral and bowel mucosa. We conducted a randomized doubleblind pilot study of rhIL-11 administered with cyclosporine/MTX prophylaxis after cytoxan/TBI conditioning and allogeneic stem cell transplantation for hematologic malignancies. Patients received rhIL-11, 50 g/kg subcutaneously daily or placebo in a 3:1 ratio. Treatment was administered prior to the start of conditioning and continued up to 21 days. The study was designed to assess safety with stopping rules for cardiac arrhythmias and mortality. Although projected to accrue 20 patients, only 13 patients (10 IL-11, three placebo) were enrolled because the early stopping rule for mortality was triggered. Of 10 evaluable patients who received IL-11, four died by day 40 and one died on day 85. Deaths were attributable to transplant-related toxicity. One of three placebo recipients died of suicide, the other two are alive. Patients receiving IL-11 had severe fluid retention and early mortality, making it impossible to determine whether IL-11 given in this schedule can reduce the rate of GVHD. Grade B-D acute GVHD occurred in two of eight evaluable patients on IL-11 and one of three patients on placebo. The primary adverse events of the study were severe fluid retention resistant to diuresis (average weight gain 9 ± 4%) and multiorgan failure in five of 10 evaluable patients. The use of IL-11 as GVHD prophylaxis in allogeneic transplantation cannot be recommended as administered in this trial.

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A study of cytokine production in acute graft-vs-host disease

Cited by 34 publications

References 16 publications

Early Intestinal Th1 Inflammation and Mucosal T Cell Recruitment During Acute Graft-Versus-Host Reaction

Early Intestinal Th1 Inflammation and Mucosal T Cell Recruitment During Acute Graft-Versus-Host Reaction

Differential anti-inflammatory effects of immunosuppressive drugs: Cyclosporin, rapamycin and FK-506 on inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and PGE2 production

A phase I/II double-blind, placebo-controlled study of recombinant human interleukin-11 for mucositis and acute GVHD prevention in allogeneic stem cell transplantation

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