Thoracic transplantationMonocyte chemoattractant protein-1 levels in bronchoalveolar lavage fluid of lung-transplanted patients treated with tacrolimus as rescue treatment for refractory acute rejection☆
Section snippets
Patients
Tacrolimus has been used at our institution for rescue treatment of nonresponsive acute lung rejection since May 1994. All patients who were alive 1 month after transplant were considered candidates for conversion to tacrolimus if they had persistent biopsy-proven AR despite treatment with a methylprednisolone bolus.
Overall, 29 lung recipients were converted from a CsA- to a tacrolimus-based immunosuppressive regimen because of refractory biopsy-proven AR. The 18 patients selected for this
Results
On the basis of a previously reported preliminary study showing encouraging clinical, immunologic, and functional results, 29 patients were converted from CsA to tacrolimus because of RAR. Eighteen of these patients were selected for the present cytokine study on the basis of the length of the follow-up and the availability of serial pre- and postconversion BAL-F samples. All patients had been on the CsA regimen for a median of 6.8 (3.7 to 8.2; 25th to 75th percentile) months after transplant.
Discussion
Future development of immunosuppressive therapy for organ transplantation must be aimed at tailoring therapy to the individual patient’s reactivity, while inducing graft acceptance by modulating the local inflammatory and immune reaction.10 However, the difficulties encountered in understanding and monitoring graft reactivity in humans hamper the understanding of these events, particularly in the field of lung transplantation. In fact, few data are presently available concerning the
References (22)
- et al.
J Heart Lung Transplant
(2002) - et al.
J Heart Lung Transplant
(2002) - et al.
Transplantation
(2002) - et al.
Am J Respir Cell Mol Biol
(2000) - et al.
Am J Respir Crit Care Med
(1999) - et al.
J Clin Invest
(2001) - et al.
J Heart Lung Transplant
(1996) Am J Respir Crit Care Med
(1995)- et al.
Clin Transplant
(1999) - et al.
Transplantation
(2001)
Am J Respir Crit Care Med
Cited by (14)
T-cell activation and transplantation tolerance
2012, Transplantation ReviewsCitation Excerpt :The importance of Tregs for transplantation was demonstrated in studies showing that Tregs reduced mouse graft-vs-host disease and could adoptively transfer tolerance to mouse allografts [27,153,154]. In humans, an important role for Tregs has been suggested by the positive correlation with Tregs number and graft survival in individuals receiving lung, kidney, liver, and islet allografts [155-159]. In addition, recent studies in mouse models engrafted with functional human immune systems have demonstrated the ability of Tregs to suppress rejection of human arterial and skin allografts by human immune systems [160,161].
Neuroantigen-specific CD8+ regulatory T-cell function is deficient during acute exacerbation of multiple sclerosis
2011, Journal of AutoimmunityCCR2 regulates monocyte recruitment as well as CD4<sup>+</sup> T <inf>h</inf>1 allorecognition after lung transplantation
2010, American Journal of TransplantationCitation Excerpt :In the lung, MCP‐1 can be produced by both stromal cells and hematopoietic cells (35,36). In humans, MCP‐1 levels are elevated in the bronchoalveolar fluid during acute lung rejection and clinical improvement of acute rejection is associated with decreases in MCP‐1 (3,37). Consistent with previous observations that MCP‐1 can be upregulated following alloantigen‐independent injury, we found that serum MCP‐1 levels were elevated in recipients of both syngeneic and allogeneic grafts as early as 24 h after transplantation (Figure 1A) (4,38–41).
Autoimmune diabetic patients undergoing allogeneic islet transplantation: are we ready for a regulatory T-cell therapy?
2009, Immunology LettersCitation Excerpt :Conversely, in solid organ transplantation the scenario is more clear. In patients transplanted with lung [38], liver [39,40], or kidney [41–44], a positive correlation between graft outcome and number of circulating nTregs has been shown. Several evidences indicate that Tr1 cells mediate transplantation tolerance.
Chemokine redundancy in BOS pathogenesis. A possible role also for the CC chemokines: MIP3-beta, MIP3-alpha, MDC and their specific receptors
2008, Transplant ImmunologyCitation Excerpt :A key role has been ascribed to pro-inflammatory cytokines such as IL-6, TNF-α and IL-1RA [5,8,9], Th-1 related factors [7,10,11] and profibrotic factors, as well as TGF-β [12,13]. Several CXC and CC chemokines have also been implicated in the pathogenesis of chronic lung rejection [7,14–20]. However, the inhibition of specific chemokine receptor-pathways (such as those related to CXCR3 or CCR2) does not entirely prevent tracheal obliteration or inflammatory infiltrate in the animal model [14,18], thus suggesting that additional factors could play a role.
- ☆
Supported by Grant 070rfm/00/01, Ministero della Sanità.