Plasma cytokines and chemokines in primary graft dysfunction post-lung transplantation

S. A. Hoffman, L. Wang, C. V. Shah, V. N. Ahya, A. Pochettino, K. Olthoff, A. Shaked, K. Wille, V. N. Lama, A. Milstone, L. B. Ware, Jonathan B Orens, A. Weinacker, E. Demissie, S. Bellamy, S. M. Kawut, W. W. Hancock, J. D. Christie

Research output: Contribution to journalArticle

Abstract

Primary graft dysfunction (PGD) after lung transplantation causes significant morbidity and mortality. We aimed to determine the role of cytokines and chemokines in PGD. This is a multicenter case-control study of PGD in humans. A Luminex analysis was performed to determine plasma levels of 25 chemokines and cytokines before and at 6, 24, 48 and 72 h following allograft reperfusion in 25 cases (grade 3 PGD) and 25 controls (grade 0 PGD). Biomarker profiles were evaluated using a multivariable logistic regression and generalized estimating equations. PGD cases had higher levels of monocyte chemotactic protein-1 (MCP-1)/chemokine CC motif ligand 2 (CCL2) and interferon (IFN)-inducible protein (IP-10)/chemokine CXC motif ligand 10 (CXCL10) (both p <0.05), suggesting recruitment of monocytes and effector T cells in PGD. In addition, PGD cases had lower levels of interleukin (IL-13) (p = 0.05) and higher levels of IL-2R (p = 0.05). Proinflammatory cytokines, including tumor necrosis factor (TNF)-α, and IFN-γ decreased to very low levels after transplant in both PGD cases and controls, exhibiting no differences between the two groups. These findings were independent of clinical variables including diagnosis in multivariable analyses, but may be affected by cardiopulmonary bypass. Profound injury in clinical PGD is distinguished by the upregulation of selected chemokine pathways, which may useful for the prediction or early detection of PGD if confirmed in future studies.

Original languageEnglish (US)
Pages (from-to)389-396
Number of pages8
JournalAmerican Journal of Transplantation
Volume9
Issue number2
DOIs
StatePublished - Feb 2009

Fingerprint

Primary Graft Dysfunction
Lung Transplantation
Chemokines
Cytokines
Interleukin-13
Chemokine CXCL10
Ligands
CXC Chemokines
CC Chemokines
Chemokine CCL2
Cardiopulmonary Bypass
Interferons
Reperfusion

Keywords

  • Chemokines
  • Cytokines
  • Lung transplantation
  • Primary graft dysfunction
  • Reperfusion injury

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Hoffman, S. A., Wang, L., Shah, C. V., Ahya, V. N., Pochettino, A., Olthoff, K., ... Christie, J. D. (2009). Plasma cytokines and chemokines in primary graft dysfunction post-lung transplantation. American Journal of Transplantation, 9(2), 389-396. https://doi.org/10.1111/j.1600-6143.2008.02497.x

Plasma cytokines and chemokines in primary graft dysfunction post-lung transplantation. / Hoffman, S. A.; Wang, L.; Shah, C. V.; Ahya, V. N.; Pochettino, A.; Olthoff, K.; Shaked, A.; Wille, K.; Lama, V. N.; Milstone, A.; Ware, L. B.; Orens, Jonathan B; Weinacker, A.; Demissie, E.; Bellamy, S.; Kawut, S. M.; Hancock, W. W.; Christie, J. D.

In: American Journal of Transplantation, Vol. 9, No. 2, 02.2009, p. 389-396.

Research output: Contribution to journalArticle

Hoffman, SA, Wang, L, Shah, CV, Ahya, VN, Pochettino, A, Olthoff, K, Shaked, A, Wille, K, Lama, VN, Milstone, A, Ware, LB, Orens, JB, Weinacker, A, Demissie, E, Bellamy, S, Kawut, SM, Hancock, WW & Christie, JD 2009, 'Plasma cytokines and chemokines in primary graft dysfunction post-lung transplantation', American Journal of Transplantation, vol. 9, no. 2, pp. 389-396. https://doi.org/10.1111/j.1600-6143.2008.02497.x
Hoffman, S. A. ; Wang, L. ; Shah, C. V. ; Ahya, V. N. ; Pochettino, A. ; Olthoff, K. ; Shaked, A. ; Wille, K. ; Lama, V. N. ; Milstone, A. ; Ware, L. B. ; Orens, Jonathan B ; Weinacker, A. ; Demissie, E. ; Bellamy, S. ; Kawut, S. M. ; Hancock, W. W. ; Christie, J. D. / Plasma cytokines and chemokines in primary graft dysfunction post-lung transplantation. In: American Journal of Transplantation. 2009 ; Vol. 9, No. 2. pp. 389-396.
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abstract = "Primary graft dysfunction (PGD) after lung transplantation causes significant morbidity and mortality. We aimed to determine the role of cytokines and chemokines in PGD. This is a multicenter case-control study of PGD in humans. A Luminex analysis was performed to determine plasma levels of 25 chemokines and cytokines before and at 6, 24, 48 and 72 h following allograft reperfusion in 25 cases (grade 3 PGD) and 25 controls (grade 0 PGD). Biomarker profiles were evaluated using a multivariable logistic regression and generalized estimating equations. PGD cases had higher levels of monocyte chemotactic protein-1 (MCP-1)/chemokine CC motif ligand 2 (CCL2) and interferon (IFN)-inducible protein (IP-10)/chemokine CXC motif ligand 10 (CXCL10) (both p <0.05), suggesting recruitment of monocytes and effector T cells in PGD. In addition, PGD cases had lower levels of interleukin (IL-13) (p = 0.05) and higher levels of IL-2R (p = 0.05). Proinflammatory cytokines, including tumor necrosis factor (TNF)-α, and IFN-γ decreased to very low levels after transplant in both PGD cases and controls, exhibiting no differences between the two groups. These findings were independent of clinical variables including diagnosis in multivariable analyses, but may be affected by cardiopulmonary bypass. Profound injury in clinical PGD is distinguished by the upregulation of selected chemokine pathways, which may useful for the prediction or early detection of PGD if confirmed in future studies.",
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AU - Hoffman, S. A.

AU - Wang, L.

AU - Shah, C. V.

AU - Ahya, V. N.

AU - Pochettino, A.

AU - Olthoff, K.

AU - Shaked, A.

AU - Wille, K.

AU - Lama, V. N.

AU - Milstone, A.

AU - Ware, L. B.

AU - Orens, Jonathan B

AU - Weinacker, A.

AU - Demissie, E.

AU - Bellamy, S.

AU - Kawut, S. M.

AU - Hancock, W. W.

AU - Christie, J. D.

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N2 - Primary graft dysfunction (PGD) after lung transplantation causes significant morbidity and mortality. We aimed to determine the role of cytokines and chemokines in PGD. This is a multicenter case-control study of PGD in humans. A Luminex analysis was performed to determine plasma levels of 25 chemokines and cytokines before and at 6, 24, 48 and 72 h following allograft reperfusion in 25 cases (grade 3 PGD) and 25 controls (grade 0 PGD). Biomarker profiles were evaluated using a multivariable logistic regression and generalized estimating equations. PGD cases had higher levels of monocyte chemotactic protein-1 (MCP-1)/chemokine CC motif ligand 2 (CCL2) and interferon (IFN)-inducible protein (IP-10)/chemokine CXC motif ligand 10 (CXCL10) (both p <0.05), suggesting recruitment of monocytes and effector T cells in PGD. In addition, PGD cases had lower levels of interleukin (IL-13) (p = 0.05) and higher levels of IL-2R (p = 0.05). Proinflammatory cytokines, including tumor necrosis factor (TNF)-α, and IFN-γ decreased to very low levels after transplant in both PGD cases and controls, exhibiting no differences between the two groups. These findings were independent of clinical variables including diagnosis in multivariable analyses, but may be affected by cardiopulmonary bypass. Profound injury in clinical PGD is distinguished by the upregulation of selected chemokine pathways, which may useful for the prediction or early detection of PGD if confirmed in future studies.

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