Tolerancia oral en artritis experimental inducida por antígeno en conejos por administración de hidrolizado de cartílago articular / Oral tolerance in antigen induced arthritis (AIA) in rabbits by administration of articular cartilage hydrolysate

La artritis reumatoide es una patología autoinmune caracterizada por inflamación poliarticular, tumefacción e inflamación que afecta a más del 1% de la población mundial. La patobiología de la artritis reumatoide involucra varias poblaciones celulares como linfocitos T, B, macrófagos y fibroblastos, así como una compleja interacción de citoquinas proinflamatorias. Las actuales terapias convencionales y biológicas no siempre funcionan o producen solo una mejora parcial. La tolerancia inmunológica es un mecanismo por el cual el sistema inmune previene la autorreactividad. El objetivo de este estudio piloto fue evaluar la eficacia de péptidos provenientes de un hidrolizado enzimático de cartílago articular extraído del tarso bovino (HCA) para el tratamiento de artritis reumatoide en un modelo de artritis reumatoide (AAE) en conejos. Los animales AAE presentaron inflamación y dolor dentro del primer mes de la inmunización primaria que fue revertida en el grupo AAE+HCA. El grupo control mostró un tejido sinovial normal sin afecciones de ningún tipo. El grupo AAE reveló un proceso inflamatorio severo con hiperplasia sinovial, infiltrado de linfocitos y proliferación vascular. El grupo tratado redujo la inflamación, proliferación linfocítica y neoangiogénesis significativamente. Los conejos artríticos incrementaron significativamente los niveles marcadores inflamatorios como óxido nítrico, interferon γ (INF-γ) y factor de necrosis tumoral α (TNF- α) respecto del control y redujeron significativamente los niveles de interleukina 4 (IL-4). El tratamiento mostró una reducción significativa de óxido nítrico, IFN-γ y TNF-α y un aumento de IL-4. Este trabajo sugiere que esta terapia podría resultar útil en el aspecto clínico y en los parámetros bioquímicos y podría inhibir específicamente la respuesta inmune. Futuros estudios con mayor número de animales y otros parámetros de laboratorio complementarios podrán brindar evidencias en este sentido (AU)

Rheumatoid arthritis is an autoimmune disease characterized by polyarticular inflammation, swelling and inflammation that affects more than 1% of the world population. The pathobiology of rheumatoid arthritis involves several cell populations as T lymphocytes, B, macrófagosy fibroblasts, and a complex proinflammatory cytokines interactions. Conventional and biologic therapies do not always work or produce only a partial improvement. Immunological tolerance is a mechanism by which the immune system prevents autoreactivity. The aim of this pilot study was to evaluate the efficacy of peptides from an from articular cartilage hydrolysate extracted of tarsus (HCA) for the treatment of rheumatoid arthritis in a model of rheumatoid arthritis (AAE) in rabbits. AAE animals showed inflammation and pain within de first month of the primary immunization that was reversed in the AAE + HCA group. The control group showed a normal unnaffected synovial tissue. The AAE group revealed an inflammatory process with synovial hyperplasia, filtering in lymphocytes and vascular proliferation. The treated group decreased significantly inflammation, lymphocyte proliferation and angiogenesis. Arthritic rabbits increased the levels inflammatory markers as nitric oxide, interferon gamma (INF-γ) and tumor necrosis factor alpha (TNF-α) compared to control and significantly reduced levels of interleukin 4 (IL-4). The treatment showed a significant reduction of nitricoxide, IFN-gamma and TNF-alpha and an increase in IL-4. This work suggests that this therapy may be useful in the clinical aspect and the biochemical and immune parameters. Future studies with larger numbers of animals and other laboratory parameters may provide additional evidence in this regard (AU)

Effects of hypophysectomy and recombinant human growth hormone on material and geometric properties and the pre- and post-yield behavior of femurs in young rats.

To study the musculoskeletal effects of hypophysectomy (Hx) and a partial replacement treatment with recombinant human growth hormone (rhGH) in rats, we determined the stiffness (elastic modulus, E) and volumetric BMD (vBMD) of cortical bone; the periosteal and endosteal perimeters, area and bending moment of inertia (xCSMI) of the cross sections, and the structural stiffness and pre- and post-yield strength of the femur diaphyses by pQCT and mechanical tests, and the gastrocnemius weight of rats that were either intact (n = 9) or Hx at 15 days of age (20). The latter were otherwise untreated (Hx controls, 4) or given 0.4 (8) or 2.0 (8) IU kg(-1) day(-1), s.c., of rhGH for 45 days starting 15 days after surgery. Hx delayed musculoskeletal development (gastrocnemius weight, bone geometric properties), thus affecting the diaphyseal stiffness and strength. It also reduced the cortical vBMD through an undefined mechanism, and increased the elastic modulus of cortical bone. The Hx also affected the correlation between bone geometric and material properties (xCSMI vs. E), suggesting an antianabolic interaction with the biomechanical control of bone modeling in response to strains caused by mechanical usage. As a result, Hx reduced the stiffness, post-yield, and ultimate strength of the diaphyses. These effects should reflect changes in bone tissue microstructure, perhaps associated with crack generation and progress, but unrelated to bone mineral mass. They are compatible with the induction of a delay in collagen turnover with associated increases in fibers' diameter and crystals' size that may have resulted from the suppression of some other hormones, such as thyroid, prolactin, or other hormones regulated by ACTH. The above doses of rhGH significantly but incompletely prevented the negative Hx effects on bone and muscle development (bone geometric properties, muscle mass). However, rhGH treatment failed to prevent the demineralizing and stiffening effect of Hx on bone tissue and the unusual effects on the post-yield strength (less clearly related to muscle development than the former). Consequently, rhGH treatment tended to preserve the natural relationship between muscle function and bone geometry but not bone strength. The effects of larger rhGH doses and the interaction of other hormones with the described effects remain to be investigated. Nevertheless, these findings would deserve special attention because they challenge the prevailing view that in endocrine-metabolic bone-weakening diseases the bone matrix always has a normal composition.