Subclinical activation of lupus nephritis by recombinant human growth hormone

Yap, Hui-Kim; Loke, Kah-Yin; Murugasu, B; Lee, Bee-Wah

doi:10.1007/s004670050421

Cited by 18 publications

(10 citation statements)

References 15 publications

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“…In this way, chronic high GH/IGF-I levels in Tg mice would produce an autoimmune-like pathology that closely resembles that described in MRL mice (Cohen & Eisenberg 1991). Furthermore, recent reports showing the anti-apoptotic effect of GH and IGF-I support this notion (Kulik & Weber 1998, Haeffner et al 1999 and would also explain the subclinical activation of lupus nephritis reported by GH administration (Yap et al 1998). However, further works need to be performed in order to understand the mechanism underlying the autoimmune-like process displayed in Tg mice.…”

Section: Discussionmentioning

confidence: 68%

“…Our results suggest that bGH Tg mice are a suitable animal model to address the pathogenesis of arthritic processes and the mechanism by which sustained high GH/IGF-I levels cause immunological disorders. In addition, the side-effects described in humans following exogenous GH administration such as oedema and a subclinical activation of lupus nephritis (Yap et al 1998) are related to the bGH Tg murine model.…”

Section: Introductionmentioning

confidence: 99%

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Transgenic mice expressing bovine GH develop arthritic disorder and self-antibodies

Ogueta¹,

Olazabal²,

Santos³

et al. 2000

Journal of Endocrinology

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We observed disability of movement in 6-month-old transgenic mice expressing the fusion gene coding for the bovine GH (bGH) under the transcriptional control of phosphoenolpyruvate carboxykinase promoter (PEPCKbGH). Histological study of the knee joint showed altered synovial and tibial articular cartilage tissues. In the cartilage the following observations were made: (i) generalized loss of the normal zonal structure and presence of clefts, and (ii) profound alterations in chondrocyte growth/ differentiation processes consistent with hypertrophy. The synovial tissue showed a reduced number of adipocytes, and a significant thickening of synovial lining tissue and pannus. These findings indicate that transgenic mice suffer damage to diarthritic joints with osteoarthritic appearance.As changes in synovial membrane in osteoarthritis are almost indistinguishable from those seen in inflammatory arthritis, we determined the potential correlation with an immunological disorder. Serological determination of selfantibodies measured as a function of age and sex showed anti-nuclear, anti-single-stranded DNA, anti-doublestranded DNA and anti-70K antibodies, and an altered immunoglobulin typing. These results suggest that transgenic mice expressing bGH develop an arthritic process which is correlated with an immune disorder. The results also indicate that these mice are a suitable animal model to study the specific role of GH-driven processes in immune cells and arthritis.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Transgenic mice expressing bovine GH develop arthritic disorder and self-antibodies

Ogueta¹,

Olazabal²,

Santos³

et al. 2000

Journal of Endocrinology

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“…They also concluded that the role of the neuroendocrine-immune system in adult SLE was, at the present time, limited to deficiencies in prolactin. Of note, two recent case reports suggested a link between growth hormone and exacerbation of lupus nephritis in a male teenager with SLE [28] as well as in juvenile SLE [29] where when growth retardation treated with growth hormone was terminated, clinical improvement in lupus symptoms was observed. These findings suggested that exogenously-administered growth hormone may result in "toxic" levels of growth hormone accompanied by lupus "flares" with progressive autoimmune dysfunction.…”

Section: Resultsmentioning

confidence: 99%

Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus

Denko

Malemud

2004

BMC Musculoskelet Disord

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BackgroundSystemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects.MethodsBasal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay.ResultsSerum growth hormone levels failed to correlate with age (r2 = 3.03) in the entire group of normal subjects (i.e. 20 – 80 years). In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r2 = 0.092). Of note, serum growth hormone was positively correlated with age (adjusted r2 = 0.269) in the 20 – 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 – 80 yrs) or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p < 0.001) in systemic lupus erythematosus patients, but only when compared to the entire group of normal subjects. Serum somatostatin levels differed from normal subjects only in older (i.e. >55 yrs) systemic lupus erythematosus patients.ConclusionsThese results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal hyperostosis and hypermobility syndrome where significantly higher serum growth hormone levels were found. Somatostatin levels in elderly systemic lupus erythematosus patients may provide a clinical marker of disease activity in these patients.

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“…GH therapy may change the disease activity in GC-treated autoimmune diseases in which T lymphocytes play a major role in controlling immune functions. Indeed, one study has indicated that GH therapy raised the activity of autoimmune diseases, including systemic lupus erythematosus treated with GC (8).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is unclear whether GH can be used safely in autoimmune disorders that are treated with GC. Indeed, a previous study has shown that GH therapy increased the disease activity in systemic lupus erythematosus patients (8). In this study, we focused on the effect of GH on peripheral T lymphocytes under GC excess.…”

mentioning

confidence: 99%

Growth hormone restores glucocorticoid‐induced T cell suppression

et al. 2001

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Growth hormone (GH) is a potent anabolic hormone, and its clinical use has been extended to the improvement of metabolic imbalance in many disease,s including autoimmune disorders treated with glucocorticoids (GCs). GH has, however, a potential action on the immune system, and this might be a demerit in GH therapy for those diseases. We report here the anti‐GC effects of GH on T lymphocytes. Human peripheral T lymphocytes (HPTLs) expressed GH receptor mRNA. GH stimulated tyrosine phosphorylation of cellular proteins, including JAK2 and STAT5b in HPTLs. GH and IGF‐I alleviated dexamethasone (Dex)‐induced suppression of [3H]thymidine incorporation into HPTLs. GH alleviated Dex‐induced apoptosis in CD4+ (positive) HPTLs. GH increased Bcl‐2 expression in CD4+ HPTLs but not in CD8+ HPTLs. In vivo, GH raised the CD4/8 ratio of T lymphocytes in rats chronically administered with Dex. These findings indicate that GH may inhibit GC‐induced apoptosis predominantly in CD4+ T lymphocytes and present important implications of GH therapy, especially for autoimmune disorders treated with GCs.

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Subclinical activation of lupus nephritis by recombinant human growth hormone

Cited by 18 publications

References 15 publications

Transgenic mice expressing bovine GH develop arthritic disorder and self-antibodies

Transgenic mice expressing bovine GH develop arthritic disorder and self-antibodies

Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus

Growth hormone restores glucocorticoid‐induced T cell suppression

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