BackgroundInterleukin-15 is an immunostimulatory cytokine overexpressed in several autoimmune and inflammatory diseases such as Rheumatoid Arthritis, psoriasis and ulcerative colitis; thus, inhibition of IL-15-induced signaling could be clinically beneficial in these disorders. Our approach to neutralize IL-15 consisted in active immunization with structurally modified human IL-15 (mhIL-15) with the aim to induce neutralizing antibodies against native IL-15. In the present study, we characterized the antibody response in Macaca fascicularis, non-human primates that were immunized with a vaccine candidate containing mhIL-15 in Aluminum hydroxide (Alum), Montanide and Incomplete Freund’s Adjuvant.ResultsImmunization with mhIL-15 elicited a specific antibodies response that neutralized native IL-15-dependent biologic activity in a CTLL-2 cell proliferation assay. The highest neutralizing response was obtained in macaques immunized with mhIL-15 adjuvanted in Alum. This response, which was shown to be transient, also inhibited the activity of simian IL-15 and did not affect the human IL-2-induced proliferation of CTLL-2 cells. Also, in a pool of synovial fluid cells from two Rheumatoid Arthritis patients, the immune sera slightly inhibited TNF-α secretion. Finally, it was observed that this vaccine candidate neither affect animal behavior, clinical status, blood biochemistry nor the percentage of IL-15-dependent cell populations, specifically CD56+ NK and CD8+ T cells.ConclusionOur results indicate that vaccination with mhIL-15 induced neutralizing antibodies to native IL-15 in non-human primates. Based on this fact, we propose that this vaccine candidate could be potentially beneficial for treatment of diseases where IL-15 overexpression is associated with their pathogenesis.

Interleukin (IL)-15 is an inflammatory cytokine that constitutes a validated therapeutic target in some immunopathologies, including rheumatoid arthritis (RA). Previously, we identified an IL-15 antagonist peptide named [K6T]P8, with potential therapeutic application in RA. In the current work, the metabolic stability of this peptide in synovial fluids from RA patients was studied. Moreover, [K6T]P8 peptide was labeled with Tc to investigate its stability in human plasma and its biodistribution pattern in healthy rats. The biological activity of [K6T]P8 peptide and its dimer was evaluated in CTLL-2 cells, using 3 different additives to improve the solubility of these peptides. The half-life of [K6T]P8 in human synovial fluid was 5.88 ± 1.73 minutes, and the major chemical modifications included peptide dimerization, cysteinylation, and methionine oxidation. Radiolabeling of [K6T]P8 with Tc showed a yield of approximately 99.8%. The Tc-labeled peptide was stable in a 30-fold molar excess of cysteine and in human plasma, displaying a low affinity to plasma proteins. Preliminary biodistribution studies in healthy Wistar rats suggested a slow elimination of the peptide through the renal and hepatic pathways. Although citric acid, sucrose, and Tween 80 enhanced the solubility of [K6T]P8 peptide and its dimer, only the sucrose did not interfere with the in vitro proliferation assay used to assess their biological activity. The results here presented, reinforce nonclinical characterization of the [K6T]P8 peptide, a potential agent for the treatment of RA and other diseases associated with IL-15 overexpression.

RESUMEN. Introducción: La técnica anestésica de elección para la artroscopía está determinada por los requerimientos quirúrgicos intraoperatorios y pretende optimizar la recuperación, el control del dolor postoperatorio y facilitar el alta precoz. Objetivo: Evaluar los resultados del bloqueo regional intraarticular con anestésicos locales en la cirugía artroscópica de rodilla. Material y métodos: Se realizó un estudio observacional, descriptivo, de corte transversal para evaluar los resultados del bloqueo regional intraarticular con anestésicos locales en la cirugía artroscópica de rodilla, en el Hospital Clínico Quirúrgico «Hermanos Ameijeiras», en el período comprendido entre febrero de 2013 y febrero de 2016. El estudio incluyó un total de 120 pacientes, distribuidos en dos grupos de 60 cada uno. Grupo AS: se utilizó anestesia subaracnoidea y Grupo AI: se realizó anestesia intraarticular con anestesia local. Resultados: El grupo etario más frecuente fue entre 60-69 años, 28.3% en el Grupo AS y 35.0% en el Grupo IA, sin diferencias significativas (p = 0.683). Predominó el sexo femenino sobre el masculino (42/18 vs 44/16), sin diferencias significativas (p = 0.839). Predominó el ASA I, en 56.7 y 43.3%, según técnica anestésica, sin diferencias significativas (p = 0.092). La rodilla derecha predominó sobre la izquierda. La entidad nosológica más frecuente fue la plica presente en 58.3% del Grupo AS y 60% en el Grupo IA (p = 0.408). La osteoartritis de rodilla, según grupos, se presentó en 46.7 % en el grupo AS y en 50.0% del grupo AI. El dolor postoperatorio estuvo presente en 21.7% del grupo AS y en 10% en el Grupo IA. Existieron diferencias significativas entre grupos (p = 0.0114). Las complicaciones según grupos, se presentaron en el doble de pacientes del grupo AS (30%) que en el Grupo IA (15%) con diferencias significativas (p = 0.049). Conclusiones: Los resultados del bloqueo regional intraarticular con anestésicos locales en la cirugía artroscópica de rodilla constituye una técnica anestésica fácil de realizar y que brinda seguridad al paciente. ABSTRACT. Introduction: The anesthetic technique of choice for arthroscopy is determined by the intraoperative surgical requirements and aims to optimize recovery, postoperative pain control and facilitate early discharge. Objective:To evaluate the results of intra-articular regional block with local anesthetics in arthroscopic knee surgery. Material and methods: An observational, descriptive, cross-sectional study was conducted to evaluate the results of the intraarticular regional block with local anesthetics in arthroscopic knee surgery at the «Hermanos Ameijeiras» Clinical Surgical Hospital, in the period between February 2013 and February 2016. The study included a total of 120 patients, distributed in two groups of 60 each. Group AS: subarachnoid anesthesia and Group AI: intra-articular regional block with local anesthetics. Results: The most frequent age group was between 60-69 years, 28.3% in group SA and 35.0% in group IA, without significant differences (...