Conference Paper

Caracterización de la actividad inmunomoduladora de diferentes quimiotipos de Cannabis sativa L enriquecidos en terpenos

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Resumen: Las enfermedades autoinmunes agrupan alrededor de 80 patologías que, en conjunto, generan un alto impacto en salud pública en el mundo y así mismo en Colombia. Esto se debe directamente a la alta prevalencia de estas, la incapacidad física y los costos que genera para el paciente y el sistema de salud (1, 2). Un ejemplo de estas enfermedades es la Artritis Reumatoide (AR), en la cual las células del sistema inmune como monocitos y macrófagos, entre otros, pierden la capacidad de reconocer las células propias del individuo y las ataca por error; generando una respuesta inmune crónica y un ambiente inflamatorio exacerbado, que conlleva a la destrucción continua de las articulaciones (3). En la búsqueda de nuevas fuentes de medicamentos que puedan utilizarse en el manejo de este tipo de padecimientos, aquellos provenientes de plantas han venido cobrando gran importancia. Este es el caso de Cannabis sativa, en la que se ha encontrado un gran potencial fitoterapéutico complementario y/o alternativo, para el manejo de diferentes enfermedades entre las que se encuentran las inflamatorias (4). En este contexto, en este trabajo se caracterizó la actividad inmunomoduladora de diferentes quimiotipos del Cannabis, sobre células proliferantes mononucleares humanas a fin de comprender su efecto en procesos inflamatorios, extrapolables a la AR. Los resultados obtenidos, revelan como la composición química de diferentes quimiotipos de la planta, afecta de diferente forma la proliferación in vitro de las células. El extracto con mayor actividad anti proliferativa fue el denominado M1, quien tiene además de los Cannabinoides tradicionales THC:CBD (1:3), una mezcla única y diferencial de terpenos como el α-Terpineol, el α-Guaiene, el Agarospirol y el Caryophyllen de los que se sabe, tienen actividad anti inflamatoria que podría explicar la mayor actividad de este extracto (5). Los análisis de viabilidad también mostraron que el extracto M1, protege a las células de la muerte por apoptosis o necrosis. Lo cual propone que el mecanismo de control de la proliferación que ejerce el extracto podría estar enfocado en la liberación de mediadores inflamatorios o en la inactivación directa de las células inmunes proliferantes.

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Previous studies have estimated a prevalence of a broad grouping of autoimmune diseases of 3.2%, based on literature review of studies published between 1965 and 1995, and 5.3%, based on national hospitalization registry data in Denmark. We examine more recent studies pertaining to the prevalence of 29 autoimmune diseases, and use these data to correct for the underascertainment of some diseases in the hospitalization registry data. This analysis results in an estimated prevalence of 7.6-9.4%, depending on the size of the correction factor used. The rates for most diseases for which data are available from many geographic regions span overlapping ranges. We also review studies of the co-occurrence of diseases within individuals and within families, focusing on specific pairs of diseases to better distinguish patterns that may result in insights pertaining to shared etiological pathways. Overall, data support a tendency for autoimmune diseases to co-occur at greater than expected rates within proband patients and their families, but this does not appear to be a uniform phenomenon across all diseases. Multiple sclerosis and rheumatoid arthritis is one disease pair that appears to have a decreased chance of coexistence.
Cannabinoids are a group of compounds present in Cannabis plant (Cannabis sativa L.). They mediate their physiological and behavioral effects by activating specific cannabinoid receptors. With the recent discovery of the cannabinoid receptors (CB1 and CB2) and the endocannabinoid system, research in this field has expanded exponentially. Cannabinoids have been shown to act as potent immunosuppressive and anti-inflammatory agents and have been shown to mediate beneficial effects in a wide range of immune-mediated diseases such as multiple sclerosis, diabetes, septic shock, rheumatoid arthritis, and allergic asthma. Cannabinoid receptor 1 (CB1) is mainly expressed on the cells of the central nervous system as well as in the periphery. In contrast, cannabinoid receptor 2 (CB2) is predominantly expressed on immune cells. The precise mechanisms through which cannabinoids mediate immunosuppression is only now beginning to be understood and can be broadly categorized into four pathways: apoptosis, inhibition of proliferation, suppression of cytokine and chemokine production and induction of T regulatory cells (T regs). Studies from our laboratory have focused on mechanisms of apoptosis induction by natural and synthetic cannabinoids through activation of CB2 receptors. In this review, we will focus on apoptotic mechanisms of immunosuppression mediated by cannabinoids on different immune cell populations and discuss how activation of CB2 provides a novel therapeutic modality against inflammatory and autoimmune diseases as well as malignancies of the immune system, without exerting the untoward psychotropic effects.
Facultad de Medicina y a la asociación Colombiana de Reumatología (ASOREUMA), por la financiación de esta iniciativa de investigación
  • A La Fundación Universitaria Juan
  • N Corpas
A la Fundación Universitaria Juan N. Corpas, Facultad de Medicina y a la asociación Colombiana de Reumatología (ASOREUMA), por la financiación de esta iniciativa de investigación. REFERENCIAS