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Transforming growth factor‐beta1 affects interleukin‐10 production in the bone marrow of patients with chronic idiopathic neutropenia
Author(s) -
Pyrovolaki Katerina,
Mavroudi Irene,
Papadantonakis Nicolas,
Velegraki Maria,
Ximeri Maria,
Kalpadakis Christina,
Gvazava Gilda,
Klaus Mirjam,
Eliopoulos George D.,
Papadaki Helen A.
Publication year - 2007
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2007.00961.x
Subject(s) - cytokine , neutropenia , cd34 , bone marrow , immunology , myeloid , transforming growth factor , medicine , progenitor cell , interleukin , haematopoiesis , stem cell , biology , microbiology and biotechnology , toxicity
Background: Chronic idiopathic neutropenia (CIN) is a bone marrow (BM) failure syndrome characterized by accelerated apoptosis of myeloid progenitor cells because of a local imbalance between pro‐inflammatory and anti‐inflammatory cytokines. In this study, we investigated the interplay among transforming growth factor‐beta1 (TGF‐β1), interleukin‐10 (IL‐10), and soluble flt‐3 ligand (sFL) within the BM of CIN patients and probed the role of these cytokines in the pathophysiology of CIN. Design: We used long‐term BM cultures (LTBMC) to evaluate TGF‐β1, IL‐10, and sFL levels in CIN patients ( n = 70) and healthy subjects ( n = 35). Cytokine levels in LTBMC supernatants were correlated with the number of circulating neutrophils and the proportion of BM CD34 + /CD33 + myeloid progenitor cells. Results: CIN patients had increased TGF‐β1 and sFL levels in LTBMCs compared with controls and individual cytokine values were found to be correlated inversely with the number of neutrophils and the proportion of CD34 + /CD33 + cells. Patients displayed low supernatant IL‐10 levels compared with controls and cytokine values were found to be correlated positively with the number of neutrophils and the proportion of CD34 + /CD33 + cells. The levels of TGF‐β1 were found to be inversely correlated with IL‐10 and positively with sFL values in LTBMC, supernatants suggesting a possible interplay among these cytokines in CIN BM. Neutralization of TGF‐β1 in LTBMCs increased IL‐10 levels significantly in patients but not in controls, while neutralization had no effect on sFL levels. Conclusion: Excessive production of TGF‐β1 within the BM microenvironment of CIN patients results in downregulation of IL‐10 and reduction of myeloid progenitor cells. Overexpression of sFL probably represents a compensatory mechanism to the low myeloid progenitor cells.