Somatostatin Treatment Attenuates Proteinuria and Prevents Weight Loss in NZB/W F1 Mice

Somatostatin, a naturally occurring neuropeptide, is an immunomodulator which inhibits humoral and cell mediated immunity as well as secretion of proinflammatory cytokines. The objective of this study was to examine the effects of a somatostatin analogue on the severity of glomerulonephritis in the...

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Bibliographic Details
Published in:Lupus 2006-01, Vol.15 (8), p.526-531
Main Authors: Paran, D, Bernheim, J, Golan, I, Caspi, D, Benchetrit, S
Format: Article
Language:English
Subjects:
Animals
Antibodies, Antinuclear - blood
Antineoplastic Agents, Hormonal - therapeutic use
Body Weight - drug effects
Cytokines
Cytokines - immunology
Disease
Disease Models, Animal
Female
Glomerulonephritis - drug therapy
Glomerulonephritis - etiology
Glomerulonephritis - pathology
Humans
Immune system
Laboratory animals
Lupus
Lupus Erythematosus, Systemic - complications
Lupus Erythematosus, Systemic - drug therapy
Lupus Erythematosus, Systemic - physiopathology
Mice
Mice, Inbred Strains
Microscopy
Neuropeptides
Octreotide - therapeutic use
Pathogenesis
Proteinuria - complications
Proteinuria - drug therapy
Proteinuria - etiology
Rheumatology
Somatostatin - analogs & derivatives
Somatostatin - therapeutic use
Spleen - cytology
Spleen - immunology
Weight Loss - drug effects
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Summary:Somatostatin, a naturally occurring neuropeptide, is an immunomodulator which inhibits humoral and cell mediated immunity as well as secretion of proinflammatory cytokines. The objective of this study was to examine the effects of a somatostatin analogue on the severity of glomerulonephritis in the female NZB/W F1 murine model of systemic lupus erythematosus (SLE). Twenty female NZB/W F1 mice were treated at 23 weeks of age with 10 mg/kg of the somatostatin analogue Sandostatin-LAR, IM every four weeks. Ten control mice received IM injection of vehicle. Mice were assessed at four-week intervals for weight change, proteinuria, anti-DNA antibodies and splenocyte cytokine profile. The mice were sacrificed at age 34.5 weeks. Kidneys were collected and evaluated by light and immunofluorescence (IF) microscopy. Spleens were collected and splenocyte intracellular cytokines were measured by FACS analysis. In the treatment group significantly less proteinuria was observed four weeks after the second somatostatin analogue injection (dipstik scale: +2.07 ± 0.95 versus. +3.5 ± 1.08, P = 0.0002). The treated mice did not lose weight while the control group lost weight over time (P = 0.016). No differences were noted between the groups in anti-DNA antibody titres, cytokine profile or the severity of lupus nephritis as assessed by light and IF microscopy. Somatostatin analogue treatment attenuated proteinuria and prevented weight loss in NZB/W F1 mice, suggesting a possible beneficial effect on renal parameters and systemic manifestations of the disease. Further studies will be needed to assess the value of somatostatin analogue treatment in lupus nephritis, utilizing higher doses, at different stages of the disease, for longer periods.
ISSN:0961-2033
1477-0962
DOI:10.1191/0961203306lu2346oa