Cytokine Dysregulation in Chronic Graft Versus Host Disease

Abstract

Copyright: Qian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Allogeneic hematopoietic stem cell transplantation is a well-established treatment for many malignant and non-malignant hematological disorders. As a frequent complication in up to 50% of all patients, graft-versus-host disease is still the main cause for morbidity and non-relapse mortality. Diagnosis is usually done clinically, even though confirmation by pathology is often used to support the clinical findings. Effective treatment requires intensified immunosuppression as early as possible. Although several promising biomarkers have been proposed for an early diagnosis, no internationally-recognized consensus has yet been established. Protein-based biomarkers represent an interesting tool since they have been recently reported to be an important regulator of various cells, including immune cells such as T cells. Therefore, we assume that protein dysregulation is important in the pathogenesis of acute graft versus host disease and their detection might be an possibility in the early diagnosis and monitoring. In this review, we aim to summarize the previous reports of protein biomarkers, focusing on the pathogenesis of the disease and possible implications in diagnostic approaches.

IL-4-producing CD8+ T cells may be an immunological hallmark of chronic GVHD

“…19,22 On the other hand, other studies favor a Th1-driven mechanism of cGVHD in both murine and human systems. [23][24][25] However, the current study could not detect any significant difference in IL-4 or IFN-g production from CD4 þ T cells between patients with and without cGVHD. Although the reason for the discrepancy in the results between the previous reports and this study is currently unknown, it might be related to the difference in the severity of cGVHD examined.…”

“…20 In addition, several reports have demonstrated that type 2 cytokines are associated with cGVHD, 21,22 whereas other studies favor the significance of Th1 balance in cGVHD. [23][24][25][26] In this study, we analyzed the cytokine production of T cells in the chronic phase of patients who underwent allo-HSCT and found that IL-4-producing CD8 þ T cells are closely associated with cGVHD.…”

Contribution of TNF-α and IL-10 gene polymorphisms to graft-versus-host disease following allo-hematopoietic stem cell transplantation

“…6,7 There have been reports that TNF-␣ is also related to the development of chronic GVHD (cGVHD). 8,9 The clinical features of cGVHD are similar to those of several autoimmune diseases, and can include autoantibody formation. [10][11][12][13] IL-10 was originally defined as a cytokine able to alter the balance of mouse Th1 and Th2 activity.…”

M-CSF attenuates severity of chronic GVHD after unrelated BMT

“…In patients with chronic GVHD, both the serum IL-10 level and IL-10 production from mononuclear cells have been shown to decrease after stimulation. [12][13][14] After stimulation with lipopolysaccharide, M-CSF-induced macrophages produce large amounts of IL-10 instead of IL-12. 15 Recent reports have shown that M-CSF induced DCs with IL-4 in a culture from human cord blood, and that these DCs produced high amounts of IL-10, but not IL-12, a pattern similar to that seen in M-CSF-induced macrophages.…”