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FRI0276 Alpha-melanocyte stimulating hormone analogue: beneficial effect in murine lupus activity
  1. D. Botte1,
  2. I. Noronha2,
  3. D. Malheiros2,
  4. S. Mello1
  1. 1Rheumatology Division of Internal Medicine
  2. 2Nephrology Division of Internal Medicine, School of Medicine of University of São Paulo, São Paulo, Brazil

Abstract

Background Alpha-Melanocyte stimulating hormone (α-MSH) is a neuropeptide that plays antiinflamatory activity through the modulation of key molecules involved in the immune response. There is no data about their role in Systemic lupus erythematosus (SLE).

Objectives The aim of the present study was to evaluate the anti-inflammatory efficacy of α-MSH in pristane-induced mice model of lupus.

Methods Lupus-like model was induced in Balb/cAn mices by a intraperitoneal injection of a single dose of 500 μl of pristane oil. After SLE induction, animals were daily treated with the MSH analog (Nle4, DPhe7-α-MSH, 1.25 mg/Kg/day ip.) or saline 0.9%. After 6 month of SLE induction animals were sacrificed and the evaluated parameters of disease were: serum IgG isotypes (ELISA), antinuclear antibodies (ANA, in Hep-2 cells). The severity of arthritis was graded by assessing the level of swelling in each paw (0.5 = swelling of toes only or very slight ankle/wrist swelling; 1 = slight swelling of paw; 2 = moderate swelling of paw; 3 = marked swelling of paw; and 4 = substantial swelling of paw). Renal lesions were evaluated in 3 m paraffin sections stained with periodic acid Schiff (PAS) and hematoxylin and eosin (H&E). Sections were graded as follows: 1 = mild focal mesangial hypercellularity alone; 2 = moderate mesangial hypercellularity; 3 = complex endocapillary hypercellularity with mild sclerosis or necrosis; 4 = severe endocapillary proliferative glomerulonephritis with necrosis/crescent formation.

Results SLE animals presented increase in seric IgG1, 2a, 2b and 3 subtypes and ANA positivity. Arthritis and renal lesion score were increased when compared with normal animals (table). The treatment of SLE animal with α-MSH promoted a significant reduction of seric IgG subtypes, as well as in the number of animals with ANA positivity. The arthritis score was 70% reduced. SLE animals treated with α-MSH shows a reduction of 20% of glomerulus cellularity and 50% of reduction of renal lesion (table).

Conclusions Our results suggest, for the first time, that the use of the α-MSH analog ameliorates the disease activity in an experimental model of lupus and seems to be a promising drug for treating SLE.

Acknowledgements # Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Disclosure of Interest: None Declared

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