Increased expression of inflammatory cytokines and adhesion molecules by alveolar macrophages of human lung allograft recipients with acute rejection: decline with resolution of rejection

Rizzo, M.; Sivasai, K. S. R.; Smith, Michael A.; Trulock, Elbert P.; Lynch, John P.; Patterson, G. Alexander; Mohanakumar, Thalachallour

doi:10.1016/s1053-2498(00)00165-0

Cited by 58 publications

(39 citation statements)

References 31 publications

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“…Increased levels of these cytokines, which may be modulated by signals mediated by TNF-R1, have been associated with rejection in previous studies (1,2,(27)(28)(29). However, we found similar levels of IFN-␥, IL-1␤, TNF-␣, IL-6, and LT␣ mRNA in both experimental groups at day 1 posttransplantation (Fig.…”

Section: Levels Of Acute Phase Response Cytokines Are Not Different Imentioning

confidence: 85%

Prolonged Allograft Survival in TNF Receptor 1-Deficient Recipients Is Due to Immunoregulatory Effects, Not to Inhibition of Direct Antigraft Cytotoxicity

McKee

DeFina

et al. 2002

The Journal of Immunology

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TNF-α and lymphotoxin (LT)α have been shown to be important mediators of allograft rejection. TNF-R1 is the principal receptor for both molecules. Mice with targeted genetic deletions of TNF-R1 demonstrate normal development of T and B lymphocytes but exhibit functional defects in immune responses. However, the role of TNF-R1-mediated signaling in solid organ transplant rejection has not been defined. To investigate this question, we performed vascularized heterotopic allogeneic cardiac transplants in TNF-R1-deficient (TNF-R1−/−) and wild-type mice. Because all allografts in our protocol expressed TNF-R1, direct antigraft effects of TNF-α and LTα were not prevented. However, immunoregulatory effects on recipient inflammatory cells by TNF-R1 engagement was eliminated in TNF-R1−/− recipients. In our study, cardiac allograft survival was significantly prolonged in TNF-R1−/− recipients. Despite this prolonged allograft survival, we detected increased levels of CD8 T cell markers in allografts from TNF-R1−/− recipients, suggesting that effector functions, but not T cell recruitment, were blocked. We also demonstrated the inhibition of multiple chemokines and cytokines in allografts from TNF-R1−/− recipients including RANTES, IFN-inducible protein-10, lymphotactin, and IL-1R antagonist, as well as altered levels of chemokine receptors. We correlated gene expression with the physiologic process of allograft rejection using self-organizing maps and identified distinct patterns of gene expression in allografts from TNF-R1−/− recipients. These findings indicate that in our experimental system TNF-α and LTα exert profound immunoregulatory effects through TNF-R1.

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Section: Levels Of Acute Phase Response Cytokines Are Not Different Imentioning

confidence: 85%

Prolonged Allograft Survival in TNF Receptor 1-Deficient Recipients Is Due to Immunoregulatory Effects, Not to Inhibition of Direct Antigraft Cytotoxicity

McKee

DeFina

et al. 2002

The Journal of Immunology

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“…Previous studies found increased levels of IL-6 expression in rejected lung transplantation patients [19] and in lung IR [20]. Recently, a study linked the high IL-6 plasma levels with cardiopulmonary damage following reperfusion [21].…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Physical Training on the Cardio-Inflammatory Disorder Induced by Lung Ischemia/Reperfusion in Rats

et al. 2010

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Our laboratory demonstrated that training program attenuated the inflammatory responses in lung ischemia/reperfusion (IR). Considering the importance of the inflammatory responses on the cardiovascular system, we evaluate the effect of physical training on the vascular responsiveness and its underlying mechanism after lung IR. Male Wistar rats were submitted to run training and lung IR. Concentration-response curves for relaxing and contracting agents were obtained. Protein expressions of SOD-1 and p47(phox), plasma nitritre/nitrate (NO (x) (-) ) and interleukin 6 (IL-6) were evaluated. A decreased in the potency for acetylcholine and phenylephrine associated with an upregulation of the p47(phox) expression were found after Lung IR as well as an increase in IL-6 and NO (x) (-) levels. Run training attenuated the vascular dysfunction that was accompanied by reduction of the p47(phox) protein expression and IL-6 levels. Our findings show the beneficial effect of training on the vascular function that was associated with reduction in inflammatory response in lung IR.

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“…Preliminary studies suggest that unlike BAL cellularity, BAL cytokine expression may show characteristic changes during acute rejection, but further studies are needed to confirm these results [14].…”

Section: The Diagnosis Of Acute Rejectionmentioning

confidence: 99%

Immunosuppressive therapy after human lung transplantation

Knoop¹,

Haverich²,

Fischer³

2004

European Respiratory Journal

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numbers of lung transplantation (LTx) were performed with or without induction therapy with antilymphocyte antibodies, monoclonal anti-CD3 antibody or anti-interleukin-2-receptor monoclonal antibodies. It remains to be established if induction therapy after LTx is beneficial or deleterious for long-term graft and patient survival.The vast majority of lung transplant recipients receive a triple-drug maintenance regimen including a calcineurin inhibitor, a cell-cycle inhibitor and steroids. Equal proportions receive cyclosporin A (CsA) and tacrolimus (Tac). There is also a trend to prescribe mycophenolate mofetil (MMF) instead of azathioprine (Aza). Steroid withdrawal is uncommon even 5 yrs after transplantation.The superiority of Tac over CsA as a maintenance agent has not been established to date, and the administration of MMF instead of Aza in combination with CsA and steroids did not improve graft or patient survival in a recent international, prospective, randomised, controlled trial.Shift from cyclosporin A to tacrolimus has emerged as the first treatment step of refractory acute rejection followed by high-dose steroids or antilymphocyte agents, total lymphoid irradiation or photopheresis. The treatment of chronic rejection remains deceptive and includes varied strategies such as modification of the maintenance regimen, addition of inhaled immunosuppressants and/or total lymphoid irradiation and photopheresis. Eur Respir J 2004; 23: 159-171.

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Increased expression of inflammatory cytokines and adhesion molecules by alveolar macrophages of human lung allograft recipients with acute rejection: decline with resolution of rejection

Cited by 58 publications

References 31 publications

Prolonged Allograft Survival in TNF Receptor 1-Deficient Recipients Is Due to Immunoregulatory Effects, Not to Inhibition of Direct Antigraft Cytotoxicity

Prolonged Allograft Survival in TNF Receptor 1-Deficient Recipients Is Due to Immunoregulatory Effects, Not to Inhibition of Direct Antigraft Cytotoxicity

Beneficial Effects of Physical Training on the Cardio-Inflammatory Disorder Induced by Lung Ischemia/Reperfusion in Rats

Immunosuppressive therapy after human lung transplantation

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