UNASSIGNED: In the face of SARS-CoV-2 infection, an uncontrolled and unregulated response of the innate immune system can cause local and multisystem organ damage, which is characteristic of patients admitted to hospitals and who die from this virus. See some of the factors involved in the severe pathological pictures of this infection, mainly in men, in articles published between 2010 and 2021 and specialized books. Research shows that age, gender, race, and blood group (specifically A), coupled with factors such as immunosenescence and comorbidities, are crucial in the severity of the disease. Finally, it is suggested that, although men and women have the same probability of becoming ill with COVID-19, men are more likely to die because they have more ACE2 receptors in plasma, greater esterase activity, produce more proinflammatory cytokines, and respond differently to hormones (testosterone favors the innate immune response more while estrogens favor the adaptive one) and to the effects of dopamine inhibitors, involved in the inflammatory response. In addition, androgen hormones regulate the TMPRSS receptor and induce metalloproteases involved in adhesion and fibrotic processes.
UNASSIGNED: Debido a la infección por SARS-CoV-2, la respuesta no controlada ni regulada del sistema inmune innato puede provocar daño orgánico local y multisistémico, que es característico en pacientes que ingresan a los hospitales y fallecen por causa del virus. Este estudio revisa algunos de los factores implicados con los cuadros patológicos graves de la infección, principalmente en hombres, de artículos publicados entre 2010 y 2021, y libros especializados. La investigación muestra que la edad, el sexo, la raza y el grupo sanguíneo (específicamente el A), aunados a diversos factores (inmunosenescencia y comorbilidades), son decisivos en la gravedad de la enfermedad. Finalmente, se plantea que, aunque los hombres y mujeres tienen la misma probabilidad de padecer COVID-19, los hombres tienen mayor posibilidad de morir, puesto que poseen más receptores ACE2 en plasma, mayor actividad de esterasas, producen más citocinas proinflamatorias y responden diferente a las hormonas (la testosterona favorece más la respuesta inmune innata mientras que los estrógenos a la adaptativa) y a los efectos de los inhibidores de dopamina implicados en la respuesta inflamatoria. Además, los andrógenos regulan al receptor TMPRSS e inducen metaloproteasas implicadas en procesos fibróticos y de adhesión.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by a wide spectrum of clinical and immunological abnormalities. New data have emerged about the role of inflammasomes in autoimmune diseases. We aimed to investigate whether basal inflammasome activation occurs in SLE patients, and whether a relationship between inflammasome-related-cytokines and disease activity exists.
METHODS: Fourteen (14) consecutive SLE patients and 13 healthy individuals, matched by sex, age and ethnicity, were included. Demographics, laboratory and clinical data were recorded. Peripheral blood mononuclear cells (PBMCs) from patients and controls were obtained and monocytes were isolated by negative selection. Purified monocytes were stimulated with LPS in the presence or absence of Caspase-1 inhibitor. CD14 and Caspase-1 expression were analyzed by flow cytometry. Cytokine levels were determined in plasma and culture supernatants by ELISA. Student\'s t test and Mann-Whitney tests were used for statistical analysis.
RESULTS: The percentage of CD14+/Caspase-1+ was significantly higher in monocytes from SLE patients compared to normal controls (p<0.01). These findings paralleled with higher plasma levels of IL-1β (p<0.05) and IL-18 (p<0.01) in those patients. Purified monocytes from SLE patients displayed a robust inflammatory response after LPS stimulation where Caspase-1, IL-1β and IL-18 were highly expressed. Plasma levels of IL-18 were also significantly higher in SLE patients with active disease (p<0.05). In addition, the production of IL-18 was reduced by 3 fold when Caspase-1 inhibitor was added to the cultures.
CONCLUSIONS: Monocytes from SLE patients exhibited increased inflammasome activation, characterized by high expression of Caspase-1, IL-1β and IL-18. Caspase-1 specific inhibitor decreased inflammasome activation (in vitro) by suppressing the production of IL-18.

Multiple sclerosis is a demyelinating inflammatory disease that affects the central nervous system. Its etiology is the result of a complex interaction between genetic and environmental factors that trigger a deregulated immune response, with the resulting inflammation and neuronal/axonal degeneration. Neuroinflammation is triggered when peripheral leukocytes migrate to the central nervous system and release cytokines such as interleukins 1 and 6 (IL-1 and 6) and tumor necrosis factor (TNF), which act on dwelling cells. The innate immune system plays an important role in the onset and progression of the disease by identifying molecular patterns associated with pathogens and damage, which modulate effector and regulatory functions of the cells where they are expressed, in order to direct the specific immune response. Th17 cells favor the disruption of the blood-brain barrier, which enables the migration of leukocytes to the central nervous system and the triggering of the inflammatory cascade; the Th1 profile (IL-1, IL-6) collaborates to perpetuate it. B-cell function is to produce antibodies and cytokines (IL-6, IL-12 and TFN). Knowledge on multiple sclerosis pathophysiology will enable the development of new therapeutic options that impact on natural history of the disease and its prognosis.
La esclerosis múltiple es una enfermedad inflamatoria desmielinizante que afecta el sistema nervioso central. Su etiología es el resultado de una compleja interacción entre factores genéticos y ambientales que desencadenan una respuesta inmune desregulada, con la consiguiente inflamación y degeneración neuronal/axonal. La neuroinflamación se desencadena cuando los leucocitos periféricos migran al sistema nervioso central y liberan citocinas como interleucinas 1 y 6 (IL-1, IL-6) y factor de necrosis tumoral (TNF), que actúan sobre células residentes del mismo. El sistema inmune innato desempeña un papel importante en el inicio y progresión de la enfermedad, mediante la identificación de patrones moleculares asociados con patógenos y daño, que modulan las funciones efectoras y reguladoras de las células donde se expresan, para dirigir la respuesta inmune específica. Las células Th17 favorecen la disrupción de la barrera hematoencefálica, que permite la migración de leucocitos al sistema nervioso central y desencadena la cascada de la inflamación; el perfil Th1 (IL-1, IL-6) colabora para perpetuarla. La función de las células B es la producción de anticuerpos y citocinas (IL-6, IL-12 y TFN). Conocer la fisiopatología de la esclerosis múltiple permitirá desarrollar nuevas opciones terapéuticas que impacten en la historia natural de la enfermedad y su pronóstico.