Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways

Article

Longbottom, E., Torrance, H., Owen, H., Fragkou, P., Hinds, C., Pearse, R. and O'Dwyer, M. 2016. Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways. Annals of Surgery. 264 (2), pp. 370-377. https://doi.org/10.1097/SLA.0000000000001484
TypeArticle
TitleFeatures of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways
AuthorsLongbottom, E., Torrance, H., Owen, H., Fragkou, P., Hinds, C., Pearse, R. and O'Dwyer, M.
Abstract

OBJECTIVE
The aim of this study was to evaluate the role of interleukin (IL)-6 pathways in postoperative immune suppression and to assess the reversibility of this phenomenon.
BACKGROUND
The postoperative period is characterized by increased IL-6 production and features of immune suppression. In vitro, IL-6 mediates anti-inflammatory effects through inhibition of interferon gamma (IFN-γ) pathways. The significance of the immunomodulatory effects of IL-6 in the clinical setting of postoperative immune suppression remains unclear.
METHODS
Patients over 45 years old undergoing elective surgery, involving the gastrointestinal tract, were recruited. IL-6 levels were assayed using an enzyme linked immunosorbent assay preoperatively, and at 24 and 48 hours. Peripheral blood mononuclear cells from healthy volunteers were cultured in perioperative serum and CD14Human Leukocyte Antigen-DR (HLA-DR) [monocyte HLA-DR (mHLA-DR)] geometric mean florescent intensity was measured in the presence and absence of IL-6 neutralizing antibody and recombinant IFN-γ.
RESULTS
Of the 108 patients, 41 developed a postoperative infection. The IL-6 levels increased 19-fold from the preoperative sample to 24 hours postoperatively (P < 0.0001). Higher IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with subsequent postoperative infectious complications. mHLA-DR mean florescent intensity fell when healthy peripheral blood mononuclear cells were cultured with postoperative serum compared with preoperative serum (P = 0.008). This decrease was prevented by the presence of IFN-γ in the culture media, but not by the presence of IL-6-neutralizing antibody.
CONCLUSIONS
IL-6 levels increase after a major surgery and are associated with an increased susceptibility to postoperative infections. Serum obtained from postoperative patients induces an immunosuppressive response, reflected in reduced mHLA-DR levels, mediated through IL-6 independent pathways and is reversible with IFN-γ. These data may have therapeutic implications for the prevention of infection in patients undergoing major surgery.

Keywordsgastrointestinal surgery; IL-6; immunoparalysis; interferon; gamma
PublisherLippincott, Williams and Wilkins
JournalAnnals of Surgery
ISSN0003-4932
Electronic1528-1140
Publication dates
Print31 Aug 2016
Publication process dates
Deposited08 Apr 2016
Accepted01 Sep 2015
Output statusPublished
Accepted author manuscript
Copyright Statement

This is a non-final version of an article published in final form in Annals of Surgery.
Longbottom, E. R., Torrance, H. D., Owen, H. C., Fragkou, P. C., Hinds, C. J., Pearse, R. M., & O’Dwyer, M. J. (2016). Features of Postoperative Immune Suppression Are Reversible With Interferon Gamma and Independent of Interleukin-6 Pathways. Annals of Surgery, 264(2), 370-377. doi:10.1097/sla.0000000000001484

Digital Object Identifier (DOI)https://doi.org/10.1097/SLA.0000000000001484
PubMed ID26445474
Web of Science identifierWOS:000380504400034
LanguageEnglish
Permalink -

https://repository.mdx.ac.uk/item/862zz

Log in to edit

Download files

Accepted author manuscript
Longbottom et al Annals of Surgery 2015.pdf

  • 44
    total views
  • 7
    total downloads
  • 2
    views this month
  • 0
    downloads this month

Export as

Related outputs

The efficacy of gemcitabine and docetaxel chemotherapy for the treatment of relapsed and refractory osteosarcoma: a systematic review and pre‐clinical study
Low, K., Foulkes, P., Hills, F., Roberts, H. and Stordal, B. 2024. The efficacy of gemcitabine and docetaxel chemotherapy for the treatment of relapsed and refractory osteosarcoma: a systematic review and pre‐clinical study. Cancer Medicine. 13 (18). https://doi.org/10.1002/cam4.70248
Identifying fibroblast growth factor receptor 3 as a mediator of periosteal osteochondral differentiation through the construction of microRNA-based interaction networks
Wells, L., Roberts, H., Luyten, F. and Roberts, S. 2023. Identifying fibroblast growth factor receptor 3 as a mediator of periosteal osteochondral differentiation through the construction of microRNA-based interaction networks. Biology. 12 (11). https://doi.org/10.3390/biology12111381
A machine learning‑based image segmentation method to quantify in vitro osteoclast culture endpoints
Davies, B.K., Hibbert, A.P., Roberts, S.J., Roberts, H., Tickner, J.C., Holdsworth, G., Arnett, T.R. and Orriss, I.R. 2023. A machine learning‑based image segmentation method to quantify in vitro osteoclast culture endpoints. Calcified Tissue International and Musculoskeletal Research. 113 (4), p. 437–448.
Establishment and characterization of single and triple‐agent resistant osteosarcoma cell lines
Low, K., Hills, F., Roberts, H. and Stordal, B. 2023. Establishment and characterization of single and triple‐agent resistant osteosarcoma cell lines. Advanced Biology. 7 (2). https://doi.org/10.1002/adbi.202200194
Overcoming chemoresistance in osteosarcoma: the role of autophagy in cell death or survival following chemotherapy
Rosa, G., Burczynska, B., Stordal, B. and Roberts, H. 2018. Overcoming chemoresistance in osteosarcoma: the role of autophagy in cell death or survival following chemotherapy. Research Degrees Students' Summer Conference. Middlesex University, London, UK 04 Sep 2018
Optimisation of a selection strategy for drug resistance osteosarcoma cell lines
Low, K., Hills, F., Roberts, H. and Stordal, B. 2018. Optimisation of a selection strategy for drug resistance osteosarcoma cell lines. Research Degrees Students' Summer Conference. Middlesex University, London, UK 04 Sep 2018
Mechanisms of apoptosis and autophagy in chemoresistant ovarian cancer cells
Bennacer, A., Roberts, H. and Stordal, B. 2018. Mechanisms of apoptosis and autophagy in chemoresistant ovarian cancer cells. Research Degrees Students' Summer Conference. Middlesex University, London, UK 04 Sep 2018
Overcoming chemoresistance in osteosarcoma: the role of autophagy in cell death or survival following chemotherapy
Rosa, G., Burczynska, B., Stordal, B. and Roberts, H. 2018. Overcoming chemoresistance in osteosarcoma: the role of autophagy in cell death or survival following chemotherapy. 2018 NCRI Cancer Conference. Glasgow, Scotland 04 - 06 Nov 2018
Optimisation of a selection strategy for drug resistance osteosarcoma cell lines
Low, K., Hills, F., Roberts, H. and Stordal, B. 2019. Optimisation of a selection strategy for drug resistance osteosarcoma cell lines. 2019 NCRI Cancer Conference. Glasgow, UK 03 - 05 Nov 2019
The role of autophagy in canine osteosarcoma chemoresistance and metastasis
Kulatheepan, Y., Baines, S., Meeson, R. and Roberts, H. 2022. The role of autophagy in canine osteosarcoma chemoresistance and metastasis. 26th Annual Technological Advances in Science, Medicine and Engineering Conference 2022. Virtual 27 - 28 Aug 2022
ATR inhibition increases sensitivity of a highly aggressive osteosarcoma cell line to cisplatin treatment
Pereira, J., Roberts, S. and Roberts, H. 2022. ATR inhibition increases sensitivity of a highly aggressive osteosarcoma cell line to cisplatin treatment. Research Students' Summer Conference. Middlesex University, Lonon, UK 22 - 23 Jun 2022
Migratory bodies express markers of tumour initiating cells and may represent an early stage of osteosarcoma sarcosphere initiation and metastasis
Paternina Martinez, D., Roberts, S. and Roberts, H. 2022. Migratory bodies express markers of tumour initiating cells and may represent an early stage of osteosarcoma sarcosphere initiation and metastasis. Research Students' Summer Conference. Middlesex University, Lonon, UK 22 - 23 Jun 2022
CRISPR/Cas9-mediated ATG7 knockout results in enhanced osteosarcoma chemosensitivity
Pears, A. and Roberts, H. 2022. CRISPR/Cas9-mediated ATG7 knockout results in enhanced osteosarcoma chemosensitivity. Bone Research Society Annual Conference. Manchester Metropolitan University, Manchester, UK 06 - 08 Jul 2022
ATR inhibition increases sensitivity of a highly aggressive osteosarcoma cell line to cisplatin treatment
Pereira, J., Roberts, S. and Roberts, H. 2022. ATR inhibition increases sensitivity of a highly aggressive osteosarcoma cell line to cisplatin treatment. Bone Research Society Annual Conference. Manchester Metropolitan University, Manchester, UK 06 - 08 Jul 2022
Migratory bodies express markers of tumour initiating cells and may represent an early stage of osteosarcoma sarcosphere initiation and metastasis
Paternina Martinez, D., Roberts, S. and Roberts, H. 2022. Migratory bodies express markers of tumour initiating cells and may represent an early stage of osteosarcoma sarcosphere initiation and metastasis. Bone Research Society Annual Conference. Manchester Metropolitan University, Manchester, UK 06 - 08 Jul 2022
Intentionality for inclusivity - the journey at Middlesex University
Roberts, H., Punev, I., Allardyce, D., Kyprianou, A., Appiah, S., Megeney, A., Calin, A., Gallacher, D. and Mill, R. 2022. Intentionality for inclusivity - the journey at Middlesex University. McGraw Hill.
Decellularised cartilage ECM culture coatings drive rapid and robust chondrogenic differentiation of human periosteal cells
Vas, W., Shah, M., Roberts, H. and Roberts, S. 2022. Decellularised cartilage ECM culture coatings drive rapid and robust chondrogenic differentiation of human periosteal cells. Bioengineering. 9 (5). https://doi.org/10.3390/bioengineering9050203
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
Klionsky, D., Roberts, H. and et al. 2021. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 17 (1), pp. 1-382. https://doi.org/10.1080/15548627.2020.1797280
Mapping human serum induced gene networks as a basis for the creation of biomimetic periosteum for bone repair
Al Hosni, R., Shah, M., Cheema, U., Roberts, H., Luyten, F. and Roberts, S. 2020. Mapping human serum induced gene networks as a basis for the creation of biomimetic periosteum for bone repair. Cytotherapy. 22 (8), pp. 424-435.
The combination of curcumin and doxorubicin shows a selective cytotoxic effect on acute myeloid leukaemia cell line
Hasan, N., Roberts, H., Ghali, L. and Appiah, S. 2018. The combination of curcumin and doxorubicin shows a selective cytotoxic effect on acute myeloid leukaemia cell line. NCRI Cancer Conference (2018). Glasgow, Scotland 04 - 06 Nov 2018
MicroRNA profiles are associated with lymphocyte count after a major traumatic injury: a potential role for immunometabolism?
Jones, T., Torrance, H., Roberts, H., Brohi, K., Barnes, M., Knight, J., Hinds, C., Ackland, G. and O'Dwyer, M. 2018. MicroRNA profiles are associated with lymphocyte count after a major traumatic injury: a potential role for immunometabolism? British Journal of Anaesthesia Research Forum. Royal College of Anaesthetists, London 30 - 31 May 2018 Elsevier. pp. e23-e24 https://doi.org/10.1016/j.bja.2018.05.027
Phytochemical modulation of apoptosis and autophagy: strategies to overcome chemoresistance in leukaemic stem cells in the bone marrow microenvironment
Owen, H., Appiah, S., Hasan, N., Ghali, L., Elayat, G. and Bell, C. 2017. Phytochemical modulation of apoptosis and autophagy: strategies to overcome chemoresistance in leukaemic stem cells in the bone marrow microenvironment. in: Zeng, B. and Zhao, K. (ed.) Neurobiology of Chinese Herb Medicine Elsevier.
Biomimetic strategies for fracture repair: engineering the cell microenvironment for directed tissue formation
Vas, W., Shah, M., Al Hosni, R., Owen, H. and Roberts, S. 2017. Biomimetic strategies for fracture repair: engineering the cell microenvironment for directed tissue formation. Journal of Tissue Engineering. 8, pp. 1-14. https://doi.org/10.1177/2041731417704791
Granulocyte macrophage colony-stimulating factor and interferon gamma act through different mechanisms in reversing post-operative immune suppression
Longbottom, E., Torrance, H., Owen, H., Hinds, C., Pearse, R. and O'Dywer, M. 2016. Granulocyte macrophage colony-stimulating factor and interferon gamma act through different mechanisms in reversing post-operative immune suppression. ESICM LIVES 2016: 29th Annual Congress of European Society of Intensive Care Medicine. Milan, Italy 01 - 05 Oct 2016 Springer. https://doi.org/10.1186/s40635-016-0098-x
Systemic inflammatory response syndrome after major abdominal surgery predicted by early upregulation of TLR4 and TLR5
Lahiri, R., Derwa, Y., Bashir, Z., Giles, E., Torrance, H., Owen, H., O'Dwyer, M., O'Brien, A., Stagg, A., Bhattacharya, S., Foster, G. and Alazawi, W. 2016. Systemic inflammatory response syndrome after major abdominal surgery predicted by early upregulation of TLR4 and TLR5. Annals of Surgery. 263 (5), pp. 1028-1037. https://doi.org/10.1097/SLA.0000000000001248
Association between early postoperatively elevated TLR-4 & TLR-5 gene expression and late nosocomial infection in elective high-risk hepato-pancreato-biliary (HPB) surgery
Pirmadjid, N., Torrance, H., Owen, H., Alazawi, W. and O'Dwyer, M. 2015. Association between early postoperatively elevated TLR-4 & TLR-5 gene expression and late nosocomial infection in elective high-risk hepato-pancreato-biliary (HPB) surgery. 2015 International Surgical Congress of the Association of Surgeons of Great Britain and Ireland. Manchester, UK 22 - 24 Apr 2015 Oxford University Press (OUP).
T-helper cell polarisation following severe polytrauma
Torrance, H., Brohi, K., Warnes, G., Owen, H., Hinds, C., Pennington, D. and O'Dwyer, M. 2015. T-helper cell polarisation following severe polytrauma. ESICM LIVES 2015: 28th Annual Congress of European Society of Intensive Care Medicine. Berlin, Germany 03 - 07 Oct 2015 Springer Open. https://doi.org/10.1186/2197-425X-3-S1-A848
Post-operative immune suppression is reversible with interferon gamma and independent of IL-6 pathways
Longbottom, E., Torrance, H., Owen, H., Hinds, C., Pearse, R. and O'Dwyer, M. 2015. Post-operative immune suppression is reversible with interferon gamma and independent of IL-6 pathways. ESICM LIVES 2015: 28th Annual Congress of European Society of Intensive Care Medicine. Berlin, Germany 03 - 07 Oct 2015 Springer Open. https://doi.org/10.1186/2197-425X-3-S1-A820
The role of micrornas in the development of hospital acquired infection in polytrauma patients
Owen, H., Torrance, H., Barnes, M., Brohi, K., Knight, J., Hinds, C. and O'Dwyer, M. 2015. The role of micrornas in the development of hospital acquired infection in polytrauma patients. ESICM LIVES 2015: 28th Annual Congress of European Society of Intensive Care Medicine. Berlin, Germany 03 - 07 Oct 2015 Springer Open. https://doi.org/10.1186/2197-425X-3-S1-A35
Changes in gene expression following trauma are related to the age of transfused packed red blood cells
Torrance, H., Vivian, M., Brohi, K., Prowle, J., Pearse, R., Owen, H., Hinds, C. and O'Dwyer, M. 2015. Changes in gene expression following trauma are related to the age of transfused packed red blood cells. Journal of Trauma and Acute Care Surgery. 78 (3), pp. 535-542. https://doi.org/10.1097/TA.0000000000000534
The perioperative immune response
O'Dwyer, M., Owen, H. and Torrance, H. 2015. The perioperative immune response. Current Opinion in Critical Care. 21 (4), pp. 336-342. https://doi.org/10.1097/MCC.0000000000000213
Critical illness-induced bone loss is related to deficient autophagy and histone hypomethylation
Owen, H., Vanhees, I., Gunst, J., Van Cromphaut, S. and Van den Berghe, G. 2015. Critical illness-induced bone loss is related to deficient autophagy and histone hypomethylation. Intensive Care Medicine Experimental. 3. https://doi.org/10.1186/s40635-015-0052-3
Epigenetic regulatory pathways involving microRNAs may modulate the host immune response following major trauma
Owen, H., Torrance, H., Jones, T., Pearse, R., Hinds, C., Brohi, K. and O'Dwyer, M. 2015. Epigenetic regulatory pathways involving microRNAs may modulate the host immune response following major trauma. Journal of Trauma and Acute Care Surgery. 79 (5), pp. 766-772. https://doi.org/10.1097/TA.0000000000000850
Humanized culture of periosteal progenitors in allogeneic serum enhances osteogenic differentiation and in vivo bone formation
Roberts, S., Owen, H., Tam, W., Solie, L., Van Cromphaut, S., Van den Berghe, G. and Luyten, F. 2014. Humanized culture of periosteal progenitors in allogeneic serum enhances osteogenic differentiation and in vivo bone formation. Stem Cells Translational Medicine. 3 (2), pp. 218-28. https://doi.org/10.5966/sctm.2012-0137
Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study
Fragkou, P., Torrance, H., Pearse, R., Ackland, G., Prowle, J., Owen, H., Hinds, C. and O'Dwyer, M. 2014. Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study. Critical Care. 18 (5). https://doi.org/10.1186/s13054-014-0541-x
Enhanced immunoreceptor tyrosine-based activation motif signaling is related to pathological bone resorption during critical illness
Vanhees, I., Gunst, J., Janssens, T., Wauters, A., Van Herck, E., Van Cromphaut, S., Van den Berghe, G. and Owen, H. 2013. Enhanced immunoreceptor tyrosine-based activation motif signaling is related to pathological bone resorption during critical illness. Hormone and Metabolic Research. 45 (12), pp. 862-9. https://doi.org/10.1055/s-0033-1351290
Critical illness-related bone loss is associated with osteoclastic and angiogenic abnormalities
Owen, H., Vanhees, I., Solie, L., Roberts, S., Wauters, A., Luyten, F., Van Cromphaut, S. and Van den Berghe, G. 2012. Critical illness-related bone loss is associated with osteoclastic and angiogenic abnormalities. Journal of Bone and Mineral Research. 27 (7), pp. 1541-1552. https://doi.org/10.1002/jbmr.1612
Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer
Dudziec, E., Miah, S., Choudhry, H., Owen, H., Blizard, S., Glover, M., Hamdy, F. and Catto, J. 2011. Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer. Clinical Cancer Research. 17 (6), pp. 1287-1296. https://doi.org/10.1158/1078-0432.CCR-10-2017
Low frequency of epigenetic events in urothelial tumours from young patients
Catto, J., Owen, H., Giedl, J., Wild, P., Fine, S., Epstein, J., Humphrey, P., Dehner, L., Amin, M., Blaszyk, H., Hughes, D., Hartmann, A. and Stoehr, R. 2010. Low frequency of epigenetic events in urothelial tumours from young patients. European Urology Supplements. 9 (2), pp. 260-261. https://doi.org/10.1016/S1569-9056(10)60798-1
Low frequency of epigenetic events in urothelial tumors in young patients
Owen, H., Giedl, J., Wild, P., Fine, S., Humphrey, P., Dehner, L., Amin, M., Epstein, J., Blaszyk, H., Hughes, D., Hartmann, A., Stoehr, R. and Catto, J. 2010. Low frequency of epigenetic events in urothelial tumors in young patients. The Journal of Urology. 184 (2), pp. 459-463. https://doi.org/10.1016/j.juro.2010.03.131
Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo
Owen, H., Ahmed, S. and Farquharson, C. 2009. Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo. Calcified Tissue International and Musculoskeletal Research. 85 (4), pp. 326-334. https://doi.org/10.1007/s00223-009-9276-0
Distinct microRNA alterations characterize high- and low-grade bladder cancer
Catto, J., Miah, S., Owen, H., Bryant, H., Myers, K., Dudziec, E., Larré, S., Milo, M., Rehman, I., Rosario, D., Di Martino, E., Knowles, M., Meuth, M., Harris, A. and Hamdy, F. 2009. Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Research. 69 (21), pp. 8472-8481. https://doi.org/10.1158/0008-5472.CAN-09-0744
Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes
Owen, H., Roberts, S., Ahmed, S. and Farquharson, C. 2008. Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes. American Journal of Physiology - Endocrinology and Metabolism. 294 (6), pp. E1023-E1034. https://doi.org/10.1152/ajpendo.00586.2007
Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1
Roberts, S., Owen, H. and Farquharson, C. 2008. Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1. Biochemical and Biophysical Research Communications. 371 (4), pp. 872-876. https://doi.org/10.1016/j.bbrc.2008.04.163
Identification and functional involvement of lipocalin 2 in glucocorticoid-induced growth retardation
Owen, H., Ahmed, S. and Farquharson, C. 2007. Identification and functional involvement of lipocalin 2 in glucocorticoid-induced growth retardation. 29th Annual Meeting of the American Society for Bone and Mineral Research. Honolulu, HI 16 - 19 Sep 2007 Wiley.
The role of P21CIP1/WAF1 in glucocorticoid induced growth retardation
Owen, H., Ahmed, S. and Farquharson, C. 2007. The role of P21CIP1/WAF1 in glucocorticoid induced growth retardation. 2007 Annual Meeting of the Bone Research Society. Southampton, UK 03 - 05 Jul 2007 Wiley.
Identification of lipocalin 2, a novel glucocorticoid responsive gene in growth plate chondrocytes
Owen, H., Ahmed, S. and Farquharson, C. 2007. Identification of lipocalin 2, a novel glucocorticoid responsive gene in growth plate chondrocytes. 2007 Annual Meeting of the Bone Research Society. Southampton, UK 03 - 05 Jul 2007 Wiley.
The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438
Owen, H., Miner, J., Ahmed, S. and Farquharson, C. 2007. The growth plate sparing effects of the selective glucocorticoid receptor modulator, AL-438. Molecular and Cellular Endocrinology. 264 (1-2), pp. 164-70. https://doi.org/10.1016/j.mce.2006.11.006
Glucocorticoids stimulate p21 expression in growth plate chondrocytes
Owen, H., Ahmed, S. and Farquharson, C. 2006. Glucocorticoids stimulate p21 expression in growth plate chondrocytes. 2006 Annual Meeting of the Bone Research Society. Southampton, UK 05 - 06 Jul 2006 Wiley.
Glucocorticoids induce lipocalin 2 gene expression in growth plate chondrocytes.
Owen, H., Ahmed, S. and Farquharson, C. 2006. Glucocorticoids induce lipocalin 2 gene expression in growth plate chondrocytes. 28th Annual Meeting of the American Society for Bone and Mineral Research. Philadelphia, PA 15 - 19 Sep 2006 Wiley.
The role of the 11 beta HSD shuttle in modulating the effects of proinflammatory cytokines on the growth plate
MacRae, V., Owen, H., Ahmed, S. and Farquharson, C. 2006. The role of the 11 beta HSD shuttle in modulating the effects of proinflammatory cytokines on the growth plate. 28th Annual Meeting of the American Society for Bone and Mineral Research. Philadelphia, PA 15 - 19 Sep 2006 Wiley.