Comparable TNF‐alpha, IFN‐gamma and GM–CSF production by purified normal marrow CD3 cells in response to horse anti‐lymphocyte and rabbit antithymocyte globulin

Abstract

In vitro priming of T cell with horse antilymphocyte globulin (HALG) results in cytokine release, and this has been associated with its clinical efficacy in patients with severe aplastic anaemia (SAA). Rabbit antithymocyte globulin (RATG) has been studied less extensively. In this study we compare the in vitro priming effect of HALG and RATG on purified normal marrow T cells: end‐points of the study were 1) levels of TNF‐alpha (TNF‐α), IFN‐gamma (IFN‐γ) GM–CSF in T cell supernatants, and 2) effect of T cell supernatants on colony formation with or without exogenous GM–CSF. TNF‐α, IFN‐γ and GM–CSF levels were comparable for HALG, RATG and phytohaemagglutinin (PHA). T cell supernatants showed comparable enhancement of colony formation in the presence of recombinant human GM–CSF (rhGM–CSF) and supported colony forming unit granulomacrophage (CFU–GM) growth in the absence of growth factor. This study shows that horse and rabbit derived ALG/ATG and PHA have a comparable in vitro priming effect on T cells: both agents should probably be tested for their clinical efficacy in SAA patients.

Incidence and differential characteristics of culture‐negative fever following pancreas transplantation with anti‐thymocyte globulin induction

“…Several cytokines are released as a result of cell lysis. In vitro experiments demonstrated that ATG induces CD3 + or CD4 + T cells and natural killer cells to produce several cytokines such as IFN‐γ, tumor necrosis factor (TNF)α, interleukin (IL)‐2, IL‐4, IL‐6, IL‐10, and granulocyte macrophage colony‐stimulating factor . Among these, IFN‐γ, TNFα, IL‐2, and IL‐6 are known endogenous pyrogens .…”

Eltrombopag Preserves the Clonogenic Potential of Hematopoietic Stem Cells During Treatment With Antithymocyte Globulin in Patients With Aplastic Anemia

“…One limitation of our study is that we could not yet identify additional factors contributing to the impaired clonogenic potential of HSPC after ATGt. TNF or interleukin‐6 might be relevant players because they are also increased after ATGt 9,23 . Moreover, TNF is known to contribute to BM failure in AA 32 .…”

“…7 Despite being beneficial for the depletion of autoreactive T cells, 8 ATG administration also results in a massive release of inflammatory cytokines such as IFN-γ, tumor necrosis factor (TNF), and other interleukins. 9,10 Eltrombopag (EPAG) induces downstream signaling of the TPO-R 11 and was recently introduced in the therapy of refractory AA due to its ability to improve hematopoiesis as monotherapy and in combination with IST. [12][13][14] A recent study has shown that EPAG enhances HSPC function by bypassing the IFN-γ-mediated perturbation of the TPO axis.…”

“…Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A (CSA) has become the standard first‐line therapy and about two thirds of the patients respond to a first treatment cycle 7 . Despite being beneficial for the depletion of autoreactive T cells, 8 ATG administration also results in a massive release of inflammatory cytokines such as IFN‐γ, tumor necrosis factor (TNF), and other interleukins 9,10 …”

“… 7 Despite being beneficial for the depletion of autoreactive T cells, 8 ATG administration also results in a massive release of inflammatory cytokines such as IFN-γ, tumor necrosis factor (TNF), and other interleukins. 9 , 10 …”