The absence of donor-derived IL-13 exacerbates the severity of acute graft-versus-host disease following allogeneic bone marrow transplantation.
Acute graft versus host disease (aGVHD) after allogeneic bone marrow transplantation (allo-BMT) predominantly involves a Th1-type cytokine response. Interestingly, the Th2-cytokine, Interleukin-13 (IL-13), produced by alloreactive donor T cells in vitro was recently shown to correlate with clinical aGVHD severity. Using an established mouse model, we show that the systemic cytokine milieu following allo-BMT with IL-13-/- donors is characterized by decreases in serum Th2 cytokines and an increase in serum TNFalpha, and ultimately correlates with higher aGVHD mortality compared to allogeneic controls. In vitro studies further demonstrate that both exogenous and T cell-derived IL-13 can regulate TNFalpha production by macrophages following lipopolysaccharide stimulation. Thus, donor-derived IL-13 may have a role in modulating inflammatory cytokine release that is associated with aGVHD.
Hildebrandt
Gerhard C
GC
Department of Hematology and Oncology, University of Regensburg Medical School, D-93053 Regensburg, Germany. gerhard.hildebrandt@klinik.uni-regensburg.de
Choi
Sung W
SW
Mueller
Gunnar
G
Olkiewicz
Krystyna M
KM
Moore
Bethany B
BB
Cooke
Kenneth R
KR
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha