Pre-treatment of transplant bone marrow cells with hydrocortisone and cyclosporin A alleviates graft-versus-host reaction in a murine allogeneic host-donor combination.

Abstract

The aim of the study was to alleviate graft-versus-host reaction (GVHR) by pre-treatment of the bone marrow (BM) transplant with hydrocortisone (HC) and cyclosporin A (CsA) in C57BL/6J (donor) --> CBA/J (recipient) mouse combination. BM cells were exposed to HC and CsA for 1 h at 37 degrees C and then injected into lethally irradiated (9.5 Gy) mice at a dose of 2 x 10(6) BM cells/mouse. Haematopoietic recovery was assessed on day 12, and survival was followed for 100 days. Combinations of 1000 microg/ml HC and 100 microg/ml CsA, and 100 microg/ml HC and 10 microg/ml CsA significantly reduced MLR and additively mitigated GVHR in vivo, achieving 40% and 26% survival rates, respectively. However, HC and CsA altered neither the peripheral blood cell counts nor in vitro and in vivo BM cell clonogenic potential. Additional studies have shown that HC and CsA blocked con A-driven differentiation of CD8+ and CD4+ CD8+ lymph node cells (LNC) and progression of LNC to S + G2/M cell cycle phases, and inhibited IL-1, IL-2 and TGF-beta while enhancing GM-CSF gene expression in BM cells. Taken together, these data indicate that the pre-treatment of the BM transplant with HC and CsA results in inactivation of GVHR effector cells and mitigation of GVHR while sparing BM repopulating capacity.