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Letters To cite Clunie GPR, Ginawi A, O’Conner P, et al. Ann Rheum Dis 2014;73:1273–1274. Received 18 November 2013 Revised 20 January 2014 Accepted 24 January 2014 Published Online First 12 February 2014
▸ http://dx.doi.org/10.1136/annrheumdis-2013-205036 Ann Rheum Dis 2014;73:1273–1274. doi:10.1136/annrheumdis-2013-204938
REFERENCES 1
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Marc V, Dromer C, Le Guennec P, et al. Magnetic resonance imaging and axial involvement in spondylarthropathies. Delineation of the spinal entheses. Rev Rhum Engl Ed 1997;64:465–73. Maksymowych WP, Jhangri GS, Fitzgerald AA, et al. A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of non-steroidal anti-inflammatory drug-refractory ankylosing spondylitis. Arthritis Rheum 2002;46:766–73. Ebetino FH, Hogan AM, Sun S, et al. The relationship between the chemistry and biological activity of the bisphosphonates. Bone 2011;49:20–33. Maksymowych WP, Dhillon SS, Park R, et al. Validation of the spondyloarthritis research consortium of Canada magnetic resonance imaging spinal inflammation index: is it necessary to score the entire spine? Arthritis Rheum 2007;57:501–7. Lambert RG, Salonen D, Rahman P, et al. Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 2007;56:4005–14. Goie The HS, Steven MM, van der Linden SM, et al. Evaluation of diagnostic criteria for ankylosing spondylitis: a comparison of the Rome, New York and modified New York criteria in patients with a positive clinical history screening test for ankylosing spondylitis. Br J Rheumatol 1985;24:242–9. Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis 2003;62:127–32. Maksymowych WP, Lambert RG, Brown LS, et al. Defining the minimally important change for spondyloarthritis research consortium of Canada spine and sacroiliac joint magnetic resonance imaging indices for ankylosing spondylitis. J Rheumatol 2012;39:1666–74.
Hydrocortisone directly promotes cholesterol accumulation in macrophages Hypercortisolism, endogenous and related to chronic therapies, is associated with increased cardiovascular risk,1 generally attributed to corticosteroid-induced salt retention and hypertension, glucose intolerance, increased appetite and obesity, and hypercholesterolaemia. We propose a novel mechanism for corticosteroids pro-atherogenic action, namely a direct promotion of foam cell formation. We investigated the direct effect of hydrocortisone on cholesterol accumulation in a model of human macrophages, based on the THP-1 cells (an acute monocyte leukaemia cell line) that can be differentiated to macrophage phenotype by phorbol 12-myristate 13-acetate treatment and is widely used in foam cell formation studies. Total cholesterol cell content was measured, according to an established protocol,2 with or without preincubation with hydrocortisone, using normal human serum as cholesterol donor, function due mainly to its low density lipoprotein (LDL) content. We found that hydrocortisone treatment significantly enhances cell cholesterol accumulation (figure 1A). Similar results were obtained when hydrocortisone was added to the normal human serum (data not shown). 1274
Figure 1 Cell cholesterol accumulation and efflux in THP-1 cells treated with hydrocortisone. (A) Cell cholesterol content after: 24 h incubation with medium (medium), 24 h incubation with normal human serum 5% (NHS), 16 h pre-incubation with hydrocortisone 100 μg/mL followed by 24 h incubation with medium (HC-medium), 16 h preincubation with hydrocortisone 100 μg/mL followed by 24 h incubation with NHS (HC-NHS). (Number of experiments=6). In cells exposed to NHS as cholesterol donor, hydrocortisone pretreatment induced a significant increase in cholesterol content (Student t test, p
Letters To cite Clunie GPR, Ginawi A, O’Conner P, et al. Ann Rheum Dis 2014;73:1273–1274. Received 18 November 2013 Revised 20 January 2014 Accepted 24 January 2014 Published Online First 12 February 2014
▸ http://dx.doi.org/10.1136/annrheumdis-2013-205036 Ann Rheum Dis 2014;73:1273–1274. doi:10.1136/annrheumdis-2013-204938
REFERENCES 1
2
3 4
5
6
7 8
Marc V, Dromer C, Le Guennec P, et al. Magnetic resonance imaging and axial involvement in spondylarthropathies. Delineation of the spinal entheses. Rev Rhum Engl Ed 1997;64:465–73. Maksymowych WP, Jhangri GS, Fitzgerald AA, et al. A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of non-steroidal anti-inflammatory drug-refractory ankylosing spondylitis. Arthritis Rheum 2002;46:766–73. Ebetino FH, Hogan AM, Sun S, et al. The relationship between the chemistry and biological activity of the bisphosphonates. Bone 2011;49:20–33. Maksymowych WP, Dhillon SS, Park R, et al. Validation of the spondyloarthritis research consortium of Canada magnetic resonance imaging spinal inflammation index: is it necessary to score the entire spine? Arthritis Rheum 2007;57:501–7. Lambert RG, Salonen D, Rahman P, et al. Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 2007;56:4005–14. Goie The HS, Steven MM, van der Linden SM, et al. Evaluation of diagnostic criteria for ankylosing spondylitis: a comparison of the Rome, New York and modified New York criteria in patients with a positive clinical history screening test for ankylosing spondylitis. Br J Rheumatol 1985;24:242–9. Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis 2003;62:127–32. Maksymowych WP, Lambert RG, Brown LS, et al. Defining the minimally important change for spondyloarthritis research consortium of Canada spine and sacroiliac joint magnetic resonance imaging indices for ankylosing spondylitis. J Rheumatol 2012;39:1666–74.
Hydrocortisone directly promotes cholesterol accumulation in macrophages Hypercortisolism, endogenous and related to chronic therapies, is associated with increased cardiovascular risk,1 generally attributed to corticosteroid-induced salt retention and hypertension, glucose intolerance, increased appetite and obesity, and hypercholesterolaemia. We propose a novel mechanism for corticosteroids pro-atherogenic action, namely a direct promotion of foam cell formation. We investigated the direct effect of hydrocortisone on cholesterol accumulation in a model of human macrophages, based on the THP-1 cells (an acute monocyte leukaemia cell line) that can be differentiated to macrophage phenotype by phorbol 12-myristate 13-acetate treatment and is widely used in foam cell formation studies. Total cholesterol cell content was measured, according to an established protocol,2 with or without preincubation with hydrocortisone, using normal human serum as cholesterol donor, function due mainly to its low density lipoprotein (LDL) content. We found that hydrocortisone treatment significantly enhances cell cholesterol accumulation (figure 1A). Similar results were obtained when hydrocortisone was added to the normal human serum (data not shown). 1274
Figure 1 Cell cholesterol accumulation and efflux in THP-1 cells treated with hydrocortisone. (A) Cell cholesterol content after: 24 h incubation with medium (medium), 24 h incubation with normal human serum 5% (NHS), 16 h pre-incubation with hydrocortisone 100 μg/mL followed by 24 h incubation with medium (HC-medium), 16 h preincubation with hydrocortisone 100 μg/mL followed by 24 h incubation with NHS (HC-NHS). (Number of experiments=6). In cells exposed to NHS as cholesterol donor, hydrocortisone pretreatment induced a significant increase in cholesterol content (Student t test, p
