Altered leucocyte trafficking and suppressed tumour necrosis factor alpha release from peripheral blood monocytes after intra-articular glucocorticoid treatment
J H Steer, D T Ma, L Dusci, G Garas, K E Pedersen, D A Joyce, J H Steer, D T Ma, L Dusci, G Garas, K E Pedersen, D A Joyce
Abstract
Objectives: A generalised transient improvement may follow intra-articular administration of glucocorticoids to patients with inflammatory arthropathy. This may represent a systemic anti-inflammatory effect of glucocorticoid released from the joint, mediated through processes such as altered leucocyte trafficking or suppressed release of pro-inflammatory cytokines. Patients, who had received intra-articular injections of glucocorticoids were therefore studied for evidence of these two systemic effects.
Methods: Patients with rheumatoid arthritis were studied. Peripheral blood leucocyte counts, tumour necrosis factor alpha (TNF alpha) release by peripheral blood monocytes, blood cortisol concentrations, and blood methylprednisolone concentration were measured for 96 hours after intra-articular injection of methylprednisolone acetate.
Results: Measurable concentrations of methylprednisolone were present in blood for up to 96 hours after injection. Significant suppression of the hypothalamic-pituitary-adrenal axis persisted throughout this time. Altered monocyte and lymphocyte trafficking, as evidenced by peripheral blood monocytopenia and lymphopenia, was apparent by four hours after injection and resolved in concordance with the elimination of methylprednisolone. Granulocytosis was observed at 24 and 48 hours. Release of TNF alpha by endotoxin stimulated peripheral blood monocytes was suppressed at four hours and thereafter. Suppression was maximal at eight hours and was largely reversed by the glucocorticoid antagonist, mifepristone.
Conclusions: After intra-articular injection of methylprednisolone, blood concentrations of glucocorticoid are sufficient to suppress monocyte TNF alpha release for at least four days and to transiently alter leucocyte trafficking. These effects help to explain the transient systemic response to intra-articular glucocorticoids. Suppression of TNF alpha is principally a direct glucocorticoid effect, rather than a consequence of other methylprednisolone induced changes to blood composition.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1752521/bin/9875.f1.jpg)
Figure 2
Lymphocyte, monocyte, and granulocyte numbers…
Figure 2
Lymphocyte, monocyte, and granulocyte numbers in peripheral blood over 96 hours after intra-articular…
Figure 3
TNFα concentrations (mean (SEM)) in…
Figure 3
TNFα concentrations (mean (SEM)) in LPS stimulated peripheral blood samples reconstituted with plasma,…
Figure 4
Blood samples taken eight hours…
Figure 4
Blood samples taken eight hours after injection release significantly less TNFα upon LPS…
- Suppression of human monocyte tumour necrosis factor-alpha release by glucocorticoid therapy: relationship to systemic monocytopaenia and cortisol suppression.Steer JH, Vuong Q, Joyce DA. Steer JH, et al. Br J Clin Pharmacol. 1997 Apr;43(4):383-9. doi: 10.1046/j.1365-2125.1997.00586.x. Br J Clin Pharmacol. 1997. PMID: 9146850 Free PMC article. Clinical Trial.
- Serum methylprednisolone levels following intra-articular injection of methylprednisolone acetate.Armstrong RD, English J, Gibson T, Chakraborty J, Marks V. Armstrong RD, et al. Ann Rheum Dis. 1981 Dec;40(6):571-4. doi: 10.1136/ard.40.6.571. Ann Rheum Dis. 1981. PMID: 7332377 Free PMC article.
- A randomized, controlled study of a single intra-articular injection of etanercept or glucocorticosteroids in patients with rheumatoid arthritis.Bliddal H, Terslev L, Qvistgaard E, Konig M, Holm CC, Rogind H, Boesen M, Danneskiold-Samsøe B, Torp-Pedersen S. Bliddal H, et al. Scand J Rheumatol. 2006 Sep-Oct;35(5):341-5. doi: 10.1080/03009740600844530. Scand J Rheumatol. 2006. PMID: 17062431 Clinical Trial.
- Inflammatory arthritis or osteoarthritis of the knee - Efficacy of intra-joint infiltration of methylprednisolone acetate versus triamcinolone acetonide or triamcinolone hexacetonide.Brazilian Medical Association; Silvinato A, Bernardo WM. Brazilian Medical Association, et al. Rev Assoc Med Bras (1992). 2017 Oct;63(10):827-836. doi: 10.1590/1806-9282.63.10.827. Rev Assoc Med Bras (1992). 2017. PMID: 29267483 Review. No abstract available.
- [Intra-articular glucocorticoid injections in joint diseases].Ostergaard M, Halberg P. Ostergaard M, et al. Ugeskr Laeger. 1999 Feb 1;161(5):582-6. Ugeskr Laeger. 1999. PMID: 9989192 Review. Danish.
- Intra-articular injection of triamcinolone acetonide sustains macrophage levels and aggravates osteophytosis during degenerative joint disease in mice.Ferrao Blanco MN, Bastiaansen Jenniskens YM, Kops N, Chavli A, Narcisi R, Botter SM, Leenen PJM, van Osch GJVM, Fahy N. Ferrao Blanco MN, et al. Br J Pharmacol. 2022 Jun;179(11):2771-2784. doi: 10.1111/bph.15780. Epub 2022 Jan 26. Br J Pharmacol. 2022. PMID: 34907535 Free PMC article.
- The systemic immunosuppressive effects of peripheral corticosteroid injections: A narrative review of the evidence in the context of COVID-19.Regan P, Elkhalifa S, Barratt P. Regan P, et al. Musculoskeletal Care. 2022 Sep;20(3):431-441. doi: 10.1002/msc.1603. Epub 2021 Dec 9. Musculoskeletal Care. 2022. PMID: 34882956 Free PMC article. Review.
- Perioperative use of intra-articular steroids during the COVID-19 pandemic.Jou E, Zhou AK, Ho JSY, Thahir A. Jou E, et al. Eur J Orthop Surg Traumatol. 2022 Oct;32(7):1225-1235. doi: 10.1007/s00590-021-03105-x. Epub 2021 Sep 1. Eur J Orthop Surg Traumatol. 2022. PMID: 34468841 Free PMC article. Review.
- The impact of intra-articular injection of diprospan at the knee joint on blood glucose levels in diabetic patients.Habib G, Khazin F, Sakas F, Hakim G, Artul S. Habib G, et al. Eur J Rheumatol. 2018 Jul;5(2):96-99. doi: 10.5152/eurjrheum.2018.17133. Epub 2018 Feb 13. Eur J Rheumatol. 2018. PMID: 30185356 Free PMC article.
- Effects of Eleutherococcus senticosus Cortex on Recovery from the Forced Swimming Test and Fatty Acid β-Oxidation in the Liver and Skeletal Muscle of mice.Sumiyoshi M, Kimura Y. Sumiyoshi M, et al. Nat Prod J. 2016 Mar;6(1):49-55. doi: 10.2174/2210315506999151207145020. Nat Prod J. 2016. PMID: 28553575 Free PMC article.
- Research Support, Non-U.S. Gov't
- Adult
- Aged
- Aged, 80 and over
- Analysis of Variance
- Anti-Inflammatory Agents / administration & dosage*
- Anti-Inflammatory Agents / blood
- Anti-Inflammatory Agents / therapeutic use
- Arthritis, Rheumatoid / drug therapy*
- Arthritis, Rheumatoid / immunology
- Cell Count
- Cells, Cultured
- Chemotaxis, Leukocyte / drug effects*
- Depression, Chemical
- Female
- Hormone Antagonists / pharmacology
- Humans
- Injections, Intra-Articular
- Lipopolysaccharides / pharmacology
- Methylprednisolone / administration & dosage
- Methylprednisolone / analogs & derivatives*
- Methylprednisolone / blood
- Methylprednisolone / therapeutic use
- Methylprednisolone Acetate
- Middle Aged
- Mifepristone / pharmacology
- Monocytes / immunology
- Tumor Necrosis Factor-alpha / metabolism*
- Anti-Inflammatory Agents
- Hormone Antagonists
- Lipopolysaccharides
- Tumor Necrosis Factor-alpha
- Mifepristone
- Methylprednisolone Acetate
- Methylprednisolone
- Full Text Sources
- Medical
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![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1752521/bin/9875.f2.jpg)
Figure 3
TNFα concentrations (mean (SEM)) in…
Figure 3
TNFα concentrations (mean (SEM)) in LPS stimulated peripheral blood samples reconstituted with plasma,…
Figure 4
Blood samples taken eight hours…
Figure 4
Blood samples taken eight hours after injection release significantly less TNFα upon LPS…
- Suppression of human monocyte tumour necrosis factor-alpha release by glucocorticoid therapy: relationship to systemic monocytopaenia and cortisol suppression.Steer JH, Vuong Q, Joyce DA. Steer JH, et al. Br J Clin Pharmacol. 1997 Apr;43(4):383-9. doi: 10.1046/j.1365-2125.1997.00586.x. Br J Clin Pharmacol. 1997. PMID: 9146850 Free PMC article. Clinical Trial.
- Serum methylprednisolone levels following intra-articular injection of methylprednisolone acetate.Armstrong RD, English J, Gibson T, Chakraborty J, Marks V. Armstrong RD, et al. Ann Rheum Dis. 1981 Dec;40(6):571-4. doi: 10.1136/ard.40.6.571. Ann Rheum Dis. 1981. PMID: 7332377 Free PMC article.
- A randomized, controlled study of a single intra-articular injection of etanercept or glucocorticosteroids in patients with rheumatoid arthritis.Bliddal H, Terslev L, Qvistgaard E, Konig M, Holm CC, Rogind H, Boesen M, Danneskiold-Samsøe B, Torp-Pedersen S. Bliddal H, et al. Scand J Rheumatol. 2006 Sep-Oct;35(5):341-5. doi: 10.1080/03009740600844530. Scand J Rheumatol. 2006. PMID: 17062431 Clinical Trial.
- Inflammatory arthritis or osteoarthritis of the knee - Efficacy of intra-joint infiltration of methylprednisolone acetate versus triamcinolone acetonide or triamcinolone hexacetonide.Brazilian Medical Association; Silvinato A, Bernardo WM. Brazilian Medical Association, et al. Rev Assoc Med Bras (1992). 2017 Oct;63(10):827-836. doi: 10.1590/1806-9282.63.10.827. Rev Assoc Med Bras (1992). 2017. PMID: 29267483 Review. No abstract available.
- [Intra-articular glucocorticoid injections in joint diseases].Ostergaard M, Halberg P. Ostergaard M, et al. Ugeskr Laeger. 1999 Feb 1;161(5):582-6. Ugeskr Laeger. 1999. PMID: 9989192 Review. Danish.
- Intra-articular injection of triamcinolone acetonide sustains macrophage levels and aggravates osteophytosis during degenerative joint disease in mice.Ferrao Blanco MN, Bastiaansen Jenniskens YM, Kops N, Chavli A, Narcisi R, Botter SM, Leenen PJM, van Osch GJVM, Fahy N. Ferrao Blanco MN, et al. Br J Pharmacol. 2022 Jun;179(11):2771-2784. doi: 10.1111/bph.15780. Epub 2022 Jan 26. Br J Pharmacol. 2022. PMID: 34907535 Free PMC article.
- The systemic immunosuppressive effects of peripheral corticosteroid injections: A narrative review of the evidence in the context of COVID-19.Regan P, Elkhalifa S, Barratt P. Regan P, et al. Musculoskeletal Care. 2022 Sep;20(3):431-441. doi: 10.1002/msc.1603. Epub 2021 Dec 9. Musculoskeletal Care. 2022. PMID: 34882956 Free PMC article. Review.
- Perioperative use of intra-articular steroids during the COVID-19 pandemic.Jou E, Zhou AK, Ho JSY, Thahir A. Jou E, et al. Eur J Orthop Surg Traumatol. 2022 Oct;32(7):1225-1235. doi: 10.1007/s00590-021-03105-x. Epub 2021 Sep 1. Eur J Orthop Surg Traumatol. 2022. PMID: 34468841 Free PMC article. Review.
- The impact of intra-articular injection of diprospan at the knee joint on blood glucose levels in diabetic patients.Habib G, Khazin F, Sakas F, Hakim G, Artul S. Habib G, et al. Eur J Rheumatol. 2018 Jul;5(2):96-99. doi: 10.5152/eurjrheum.2018.17133. Epub 2018 Feb 13. Eur J Rheumatol. 2018. PMID: 30185356 Free PMC article.
- Effects of Eleutherococcus senticosus Cortex on Recovery from the Forced Swimming Test and Fatty Acid β-Oxidation in the Liver and Skeletal Muscle of mice.Sumiyoshi M, Kimura Y. Sumiyoshi M, et al. Nat Prod J. 2016 Mar;6(1):49-55. doi: 10.2174/2210315506999151207145020. Nat Prod J. 2016. PMID: 28553575 Free PMC article.
- Research Support, Non-U.S. Gov't
- Adult
- Aged
- Aged, 80 and over
- Analysis of Variance
- Anti-Inflammatory Agents / administration & dosage*
- Anti-Inflammatory Agents / blood
- Anti-Inflammatory Agents / therapeutic use
- Arthritis, Rheumatoid / drug therapy*
- Arthritis, Rheumatoid / immunology
- Cell Count
- Cells, Cultured
- Chemotaxis, Leukocyte / drug effects*
- Depression, Chemical
- Female
- Hormone Antagonists / pharmacology
- Humans
- Injections, Intra-Articular
- Lipopolysaccharides / pharmacology
- Methylprednisolone / administration & dosage
- Methylprednisolone / analogs & derivatives*
- Methylprednisolone / blood
- Methylprednisolone / therapeutic use
- Methylprednisolone Acetate
- Middle Aged
- Mifepristone / pharmacology
- Monocytes / immunology
- Tumor Necrosis Factor-alpha / metabolism*
- Anti-Inflammatory Agents
- Hormone Antagonists
- Lipopolysaccharides
- Tumor Necrosis Factor-alpha
- Mifepristone
- Methylprednisolone Acetate
- Methylprednisolone
- Full Text Sources
- Medical
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1752521/bin/9875.f3.jpg)
Figure 4
Blood samples taken eight hours…
Figure 4
Blood samples taken eight hours after injection release significantly less TNFα upon LPS…
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/1752521/bin/9875.f4.jpg)
References
- Eur J Clin Invest. 1994 Nov;24(11):773-7
- Circulation. 1997 Jul 1;96(1):295-301
- J Exp Med. 1970 Mar 1;131(3):429-42
- J Exp Med. 1973 Jan 1;137(1):10-21
- Br J Haematol. 1973 Mar;24(3):275-85
- J Clin Invest. 1974 Jan;53(1):240-6
- J Clin Invest. 1975 Jan;55(1):22-32
- Ann Rheum Dis. 1981 Dec;40(6):571-4
- Hybridoma. 1987 Jun;6(3):305-11
- Arthritis Rheum. 1988 Mar;31(3):315-24
- Br J Clin Pharmacol. 1988 Dec;26(6):709-13
- Lymphokine Res. 1990 Summer;9(2):147-53
- Am J Respir Cell Mol Biol. 1992 Jan;6(1):75-81
- Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):9991-5
- Mol Pharmacol. 1993 Feb;43(2):176-82
- J Clin Pharmacol. 1993 Feb;33(2):115-23
- Rheumatol Int. 1993;12(6):217-20
- Endocrinology. 1993 Nov;133(5):1922-33
- Ann Intern Med. 1993 Dec 15;119(12):1198-208
- BMJ. 1993 Nov 20;307(6915):1329-30
- J Neuroimmunol. 1994 Feb;50(1):71-6
- Arthritis Rheum. 1995 Feb;38(2):151-60
- Am J Clin Pathol. 1995 Feb;103(2):167-70
- J Leukoc Biol. 1995 Mar;57(3):379-86
- J Investig Med. 1995 Feb;43(1):68-77
- Curr Opin Rheumatol. 1995 May;7(3):229-34
- Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8016-20
- Genet Anal. 1995 Mar;12(1):39-43
- Endocrinology. 1995 Sep;136(9):4133-8
- Am J Respir Cell Mol Biol. 1996 Jul;15(1):97-106
- Eur J Immunol. 1996 Nov;26(11):2758-63
- J Immunol. 1997 Apr 15;158(8):3836-44
- J Immunol. 1997 May 15;158(10):5007-16
- Br J Clin Pharmacol. 1997 Apr;43(4):383-9
- Circ Shock. 1994 Aug;43(4):179-84
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