[Delta-9-tetrahydrocannabinol-cannabidiol in the treatment of spasticity in chronic spinal cord injury: a clinical experience]. / Delta-9-tetrahidrocannabinol-cannabidiol en el tratamiento de la espasticidad en la lesion medular cronica: una experiencia clinica.

INTRODUCTION: Spasticity in chronic spinal cord injury is a condition that can have negative repercussions on the patient's quality of life. Its treatment is complex and sometimes the outcome is insufficient. Cannabinoids have recently been used in multiple sclerosis to successfully treat spasticity that is refractory to other therapies. AIM: To quantify the clinical response of a group of patients with spastic chronic spinal cord injury to the orally administered drug delta-9-tetrahydrocannabinol-cannabidiol (Sativex ®) as medication for use in special situations. PATIENTS AND METHODS: The research consists of a six-month observational study in patients with chronic spinal cord injuries with refractory spasticity. The variables collected were: modified Ashworth scale, Penn spasm frequency scale, Numeric Rating Scale, and Visual Analogue Scale for pain. Additionally, clinical variables and side effects of the treatment were also collected. RESULTS: Fifteen patients took part in this study. A significant improvement was observed on three of the scales recorded: modified Ashworth scale (z = -2.97; p = 0.003), Penn spasm frequency scale (z = -2.76; p = 0.006) and Numeric Rating Scale (z = -3.21; p = 0.001). The use of the drug was withdrawn in two patients due to side effects. CONCLUSIONS: Sativex can be considered an alternative in patients with spasticity associated with chronic spinal cord injury for whom other therapeutic measures have been insufficient. Further studies need to be conducted before the use of this drug can be recommended and so as to define a complete profile of its long-term side effects.

TITLE: Delta-9-tetrahidrocannabinol-cannabidiol en el tratamiento de la espasticidad en la lesion medular cronica: una experiencia clinica.Introduccion. La espasticidad en la lesion medular cronica es una condicion que puede repercutir negativamente en la calidad de vida del paciente. Su tratamiento es complejo y, en ocasiones, el resultado es insuficiente. Recientemente, en la esclerosis multiple los cannabinoides se han empleado con exito en el tratamiento de la espasticidad refractaria a otras terapias. Objetivo. Cuantificar la respuesta clinica de un grupo de pacientes con lesion medular cronica espastica al farmaco delta-9-tetrahidrocannabinol-cannabidiol (Sativex ®), de administracion oral, como medicamento de uso en situaciones especiales. Pacientes y metodos. Estudio observacional durante seis meses en lesionados medulares cronicos con espasticidad refractaria. Las variables recogidas fueron: escala modificada de Ashworth, escala de frecuencia de espasmos de Penn, Numeric Rating Scale y escala visual analogica del dolor. De forma adicional se recogieron variables clinicas y efectos secundarios del tratamiento. Resultados. Quince pacientes tomaron parte en el estudio. Se observo mejoria significativa en tres de las escalas registradas: escala de Ashworth modificada (z = -2,97; p = 0,003), escala de frecuencia de espasmos de Penn (z = -2,76; p = 0,006) y Numeric Rating Scale (z = -3,21; p = 0,001). Se suspendio el uso del farmaco en dos pacientes por efectos secundarios. Conclusiones. Sativex se muestra como una alternativa en pacientes con espasticidad asociada a lesion medular cronica, en las que otras medidas terapeuticas resultan insuficientes. Son necesarios mas estudios para recomendar el uso de este farmaco y definir un perfil completo de sus efectos adversos a largo plazo.

Risk factors in iatrogenic spinal cord injury.

STUDY DESIGN: In the last years, there has been a change in the aetiology of spinal cord injury. There has been an increase in the number of elderly patients with spinal cord injuries caused by diseases or medical procedures. OBJECTIVE: The aim of this study is to investigate the frequency of the occurrence of iatrogenic spinal cord injury in our unit. The secondary aim is to study what variables can be associated with a higher risk of iatrogenesis. METHODS: A retrospective, descriptive, observational study of patients with acute spinal cord injury admitted from June 2009 to May 2014 was conducted. The information collected included the patient age, aetiology, neurological level and grade of injury when admitted and when discharged, cardiovascular risk factors, a previous history of depression and any prior treatment with anticoagulant or antiplatelet drugs. We applied a logistic regression. The grade of statistical significance was established as P<0.05. RESULTS: In total, 265 patients were included. In 48 of the cases, the cause was iatrogenic (18.18%±4.6% IC). The most frequent level of injury was the thoracic level (48%). The main aetiology of spinal cord injury caused by iatrogenesis was surgery for degenerative spine disease, in patients under the age of 30 were treated with intrathecal chemotherapy. CONCLUSIONS: Iatrogenic spinal cord injury is a frequent complication. A statistically significant association between a patient history of depression and iatrogenic spinal cord injury was found as well as with anticoagulant and antiplatelet drug use prior to iatrogenic spinal cord injury.

Mujer con dolor cervical súbito y deterioro neurológico / Woman with sudden neck pain and neurological impairment

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Adaptation and validation of the Spanish self-report version of the Spinal Cord Independence Measure (SCIM III).

STUDY DESIGN: This is a cross-sectional validation study. OBJECTIVE: The objective of this study was to adapt and validate a self-report version of the Spinal Cord Independence Measure (SCIM III) for the Spanish population. METHODS: A cross-cultural adaptation of the self-report version of the SCIM III for the Spanish population was performed on the basis of international guidelines. A total of 100 patients with spinal cord injury (SCI) were recruited. A team of healthcare professionals administered the SCIM III by observation. In addition, the patients completed the Spanish self-report version (eSCIM-SR). Data from both questionnaires were analysed jointly. RESULTS: A high correlation was observed between SCIM III and eSCIM-SR. Lin's concordance correlation coefficient for the global score was 0.998 (95% confidence interval: 0.997, 0.998), and the subscale scores were 0.988 (0.982, 0.992) for self-care, 0.992 (0.988, 0.995) for respiration and sphincter management and 0.997 (0.995, 0.998) for Mobility. Bland-Altman plots showed a small bias of -0.32 (95% limits of agreement: -3.01, 2.37). The estimated bias was low in all three domains, with values of -0.22 (-2.12, 1.68), -0.1 (-2.02, 1.82) and -0.03 (-1.69, 1.63) for the self-care, respiration and sphincter management and mobility subscales, respectively. CONCLUSION: Our study validates the eSCIM-SR as a tool for the functional assessment of patients with SCI, principally in the outpatient setting.

Interés del uso clínico del tensor de difusión en la planificación del tratamiento rehabilitador en pacientes tras el primer ictus / Importance of the clinical use of the diffusion tensor in planning rehabilitation treatment in patients after the first stroke

Objetivo. Contrastar la utilidad predictiva de la RM en la modalidad del tensor de difusión (TD) en una muestra de pacientes que han presentado un ictus. Material y método. Estudio prospectivo sobre 7 pacientes de ambos sexos, ingresados para tratamiento rehabilitador intensivo tras primer episodio de ictus isquémico. Protocolo: 1) Valoración habilidades motoras: índice motor, prueba de control de tronco; 2) Capacidad de la marcha: functional assessment categories y capacidad funcional: índice de Barthel y Functional Independence Measure (FIM); 3) Estudio tractográfico: media y desviación estándar de fracción de anisotropía (FA) y coeficiente de difusión (CDA) aparente en cápsula interna, corona radiata y tracto protuberancial derecho e izquierdo; y 4) Estudio estadístico: representación de las relaciones 2 a 2 entre todas las variables en estudio, y comprobación de cada posible relación con modelo de regresión simple (lineal o logístico). Se han incluido resultados con un valor de p menor de 0,2. Resultados. Las relaciones con significatividad 2 a 2 son: 1) índice motor de la extremidad superior y FA en el tracto protuberancial; 2) índice motor de la extremidad inferior y la FA a nivel de la corona radiata; 3) FIM motor y cognitivo con el CDA aparente a nivel de la corona radiata; 4) FIM motor y cognitivo con la FA en el tracto protuberancial; 5) FIM cognitivo y la FA a nivel de la corona radiata; 6) FIM total con la FA en la cápsula interna; y 7) tracto protuberancial, así como con el CDA en el tracto protuberancial. Los resultados representan las conclusiones preliminares del empleo del TD en una muestra reducida de pacientes atendidos en una unidad de neurorrehabilitación en los que consideramos de utilidad el uso del TD en la predicción evolutiva del ictus (AU)

Objective. To compare the predictive value of the MR diffusion tensor (DT) imaging modality in a sample of stroke patients. Material and method. A prospective study was conducted on 7 inpatient subjects of both genders who were undergoing intensive rehabilitation after a first ischemic stroke. The protocol included: 1) motor skills evaluation by Motor Index, Trunk Control Test; 2) Walking capacity: functional assessment categories and functional capacity: Barthel Index and Functional Independence Measure (FIM); 3) Tractography study: mean and standard deviation for fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in internal capsule, corona radiata and right and left pontine tract; 4) Statistical analysis: projection of the data into a two-dimensional scatterplot matrix; verification of every possible link with a simple regression model (linear or logistic). Results with P-value <0.2 are included. Results. The relations with two pairs of variables that are significant are: 1) upper extremity motor skill and FA values in the pontine tract; 2) lower extremity motor skill and FA values at the corona radiate; 3) motor and cognitive FIM with ADC at the corona radiate; 4) motor and cognitive FIM with FA in the pontine tract; 5) Cognitive FIM and FA at the corona radiate; 6) FIM total and FA at the internal capsule and pontine tract and, 7) total FIM and ADC in the pontine tract. The results represent the preliminary findings of the use of DT in a small sample of stroke patients in a neurorehabilitation unit. We consider DT to be useful in the evolutive prediction of stroke (AU)

Effects of cooling and freezing storage on the stability of bioactive factors in human colostrum.

Breast milk constitutes the best form of newborn alimentation because of its nutritional and immunological properties. Banked human milk is stored at low temperature, which may produce losses of some bioactive milk components. During lactation, colostrum provides the requirements of the newborn during the first days of life. The aim of this study was to evaluate the effect of cooling storage at 4°C and freezing storage at -20°C and -80°C on bioactive factors in human colostrum. For this purpose, the content of IgA, growth factors such as epidermal growth factor, transforming growth factor (TGF)-ß1 and TGF-ß2, and some cytokines such as IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α, and its type I receptor TNF-RI, were quantified. Some colostrum samples were stored for 6, 12, 24, and 48 h at 4°C and others were frozen at -20°C or -80°C for 6 and 12 mo. We quantified IgA, epidermal growth factor, TGF-ß1, and TGF-ß2 by indirect ELISA. Concentrations of IL-6, IL-10, and TNF-α cytokines, IL-8 chemokine, and TNF-RI were measured using the BD Cytometric Bead Array (BD Biosciences, Erembodegem, Belgium). Bioactive immunological factors measured in this study were retained in colostrum after cooling storage at 4°C for at least 48h, with the exception of IL-10. None of the initial bioactive factor concentrations was modified after 6 mo of freezing storage at either -20°C or -80°C. However, freezing storage of colostrum at -20°C and -80°C for 12 mo produced a decrease in the concentrations of IgA, IL-8, and TGF-ß1. In summary, colostrum can be stored at 4°C for up to 48 h or at -20°C or -80°C for at least 6 mo without losing its immunological properties. Future studies are necessary to develop quality assurance guidelines for the storage of colostrum in human milk banks, and to focus not only on the microbiological safety but also on the maintenance of the immunological properties of colostrum.

Maintenance of breast milk Immunoglobulin A after high-pressure processing.

Human milk is considered the optimal nutritional source for infants. Banked human milk is processed using low-temperature, long-time pasteurization, which assures microbial safety but involves heat denaturation of some desirable milk components such as IgA. High-pressure processing technology, the subject of the current research, has shown minimal destruction of food macromolecules. The objective of this study was to investigate the influence of pressure treatments on IgA content. Moreover, bacterial load was evaluated after pressure treatments. The effects of high-pressure processing on milk IgA content were compared with those of low-temperature, long-time pasteurization. Mature human milk samples were heat treated at 62.5 degrees C for 30min or pressure processed at 400, 500, or 600MPa for 5min at 12 degrees C. An indirect ELISA was used to measure IgA in human milk whey obtained after centrifugation at 800xg for 10min at 4 degrees C. All 3 high-pressure treatments were as effective as low-temperature, long-time pasteurization in reducing the bacterial population of the human milk samples studied. After human milk pressure processing at 400MPa, 100% of IgA content was preserved in milk whey, whereas only 72% was retained in pasteurized milk whey. The higher pressure conditions of 500 and 600MPa produced IgA retention of 87.9 and 69.3%, respectively. These results indicate that high-pressure processing at 400MPa for 5min at 12 degrees C maintains the immunological protective capacity associated with IgA antibodies. This preliminary study suggests that high-pressure processing may be a promising alternative to pasteurization in human milk banking.

[The bowel: a key component of the immune system]. / El intestino: pieza clave del sistema inmunitario.

The gut is constantly exposed to a high antigenic load coming from the diet and commensal bacteria. The Gut-Associated Lymphoid Tissue (GALT) constitutes the most extensive and complex part of the immune system and is capable of efficiently distinguishing invasive pathogens from innocuous antigens. The knowledge of its unique structure consisting on organised tissue, inductor of the immune response (Peyer's patches and mesenteric lymph nodes), and diffused tissue, effector of the immune response (intraepithelial lymphocytes and lamina propria lymphocytes), allow us to understand the development and regulation of the immune response in the gut and how this one can be extended to the rest of the organism.

El intestino: pieza clave del sistema inmunitario / No disponible

El intestino se halla expuesto constantemente a una elevada cargaantigénica procedente de la dieta y de bacterias comensales. Eltejido linfoide asociado al intestino (Gut-Associated Lymphoid Tissue,GALT) constituye la parte más extensa y compleja del sistemainmunitario y es capaz de discriminar de forma eficaz entre patógenosinvasivos y antígenos inocuos. El conocimiento de su particularsubdivisión en tejido organizado, inductor de la respuesta inmunitaria(placas de Peyer y ganglios linfáticos mesentéricos), y tejido difuso,efector de la respuesta inmunitaria (linfocitos intraepiteliales ylinfocitos de lámina propia), nos permite comprender cómo se desarrollay regula la respuesta inmunitaria en el intestino y como estapuede extenderse al resto del organismo

The gut is constantly exposed to a high antigenic load comingfrom the diet and commensal bacteria. The Gut-Associated LymphoidTissue (GALT) constitutes the most extensive and complexpart of the immune system and is capable of efficiently distinguishinginvasive pathogens from innocuous antigens. The knowledgeof its unique structure consisting on organised tissue, inductorof the immune response (Peyer’s patches and mesentericlymph nodes), and diffused tissue, effector of the immune response(intraepithelial lymphocytes and lamina propria lymphocytes),allow us to understand the development and regulation ofthe immune response in the gut and how this one can be extended to the rest of the organism (AU)

Spleen lymphocyte function modulated by a cocoa-enriched diet.

Previous studies have shown the down-regulating in vitro effect of cocoa flavonoids on lymphocyte and macrophage activation. In the present paper, we report the capacity of a long-term rich cocoa diet to modulate macrophage cytokine secretion and lymphocyte function in young rats. Weaned rats received natural cocoa (4% or 10% food intake), containing 32 mg flavonoids/g, for 3 weeks. Spleen immune function was then evaluated through the analysis of lymphocyte composition, their proliferative response and their ability to secrete cytokines and Ig. In addition, the status of activated peritoneal macrophages was established through tumour necrosis factor (TNF)-alpha secretion. The richest cocoa diet (10%) caused a reduction of TNF-alpha secretion by peritoneal macrophages showing anti-inflammatory activity. Similarly, although a 10% cocoa diet increased lymphocyte proliferation rate, it down-regulated T helper 2 (Th2)-related cytokines and decreased Ig secretion. These changes were accompanied by an increase in spleen B cell proportion and a decrease in Th cell percentage. In summary, these results demonstrate the functional activity of a cocoa-high dosage in down-regulating the immune response that might be beneficial in hypersensitivity and autoimmunity.

Linfedema crónico de miembros inferiores en gigantismo por tumor hipofisario / Chronic lymphedema of the lower limbs in gigantism due to hypophysial tumor

Se presenta el caso de una mujer de 44 años con linfedema-elefantiasis en miembros inferiores grado IV, de 20 años de evolución, con múltiples complicaciones cutáneas, en el contexto de gigantismo que apareció en la infancia como consecuencia de un tumor hipofisario productor de hormona de crecimiento. La producción excesiva de hormona de crecimiento ocasiona el crecimiento excesivo de tejidos óseos, cartilaginosos, vísceras, partes blandas, así como alteraciones endocrinas y cardiovasculares. Los resultados del tratamiento descongestivo de linfedema, con drenaje linfático manual, presoterapia multicompartimental, vendajes compresivos y cinesiterapia, seguido de una terapia de mantenimiento, fueron satisfactorios, permaneciendo estable en la actualidad. (AU)

Prevention of adjuvant arthritis by the W3/25 anti-CD4 monoclonal antibody is associated with a decrease of blood CD4(+)CD45RC(high) T cells.

Imbalance between Th1 and Th2 functions is considered to play a key role in the induction and development of several autoimmune diseases, and the correction of that imbalance has led to effective therapies of some experimental pathologies. To examine whether CD4(+)CD45RC(high) (Th1-like) and CD4(+)CD45RC(low) (Th2-like) lymphocytes play a role in the pathogenesis of adjuvant arthritis (AA) and in its prevention by anti-CD4 antibody, CD45RC expression on CD4(+) T cells was determined in arthritic rats and in animals treated with an anti-CD4 MoAb (W3/25) during the latency period of AA. The phenotype of regional lymph node lymphocytes from arthritic rats in the active phase of the disease was determined by flow cytometry. Peripheral blood lymphocytes from rats treated with W3/25 MoAb were also analysed for 2 weeks after immunotherapy finished. IgG2a and IgG1 isotypes of sera antibodies against the AA-inducing mycobacteria, considered to be associated with Th1 and Th2 responses, respectively, were also determined by ELISA techniques. Fourteen days after arthritis induction, regional lymph nodes presented an increase in CD4+CD45RC(high) T cell proportion. Preventive immunotherapy with W3/25 MoAb inhibited the external signs of arthritis and produced a specific decrease in blood CD4(+)CD45RC(high) T cells and a diminution of antibodies against mycobacteria, more marked for IgG2a than for IgG1 isotype. These results indicate a possible role of CD4(+)CD45RC(high) T lymphocytes in the pathogenesis of AA, and suggest that the success of anti-CD4 treatment is due to a specific effect on CD4(+)CD45RC(high) T subset that could be associated with a decrease in Th1 activity.

Immunohistochemical study of lymphoid tissues in adjuvant arthritis (AA) by image analysis; relationship with synovial lesions.

The aim of this study was to examine leucocyte populations in lymphoid organs during AA and to ascertain the relationship with lesions in synovial joints. Popliteal lymph nodes, spleen and knee synovial membranes were removed from both healthy and AA rats at intervals of 3-4 days over a 3-week period. Cryostat sections were stained with MoAbs directed against lymphocyte and macrophage subpopulations, and studied by image analysis. Throughout the arthritic period, high numbers of ED1+ and ED3+ macrophages were seen in both lymphoid compartments and intercellular adhesion molecule-1 (ICAM-1) expression also increased in some zones of lymph nodes and spleen. The percentages of CD4+ and CD8+ cells rose in the splenic zones studied but fell in the lymph node cortex. Very few natural killer (NK) cells were found in lymphoid tissues, but the number rose after AA induction. In synovia from AA rats, ED2+ macrophages proliferated but alpha/beta T cell infiltration was only occasionally observed, accompanied by ED1+ cells and ICAM-1 expression. In conclusion, synovitis developing after AA induction seems to be caused directly by macrophages and indirectly by lymphocytes placed both in popliteal lymph nodes and spleen.

An image analysis strategy to determine the distribution of cell types in spleen sections.

An image analysis strategy was designed to objectively determine distribution patterns of cell types in spleen sections. The strategy was applied to rat spleen cryostat sections that were strained immunohistochemically by means of monoclonal antibodies against different populations of lymphocytes and macrophages. The strategy revealed three segments of the spleen beginning in the middle of a central arteriole and ending within the red pulp. In each of these segments, three consecutive zones were established: the white pulp, the marginal zone, and the red pulp. In each tissue section, three segments were selected starting in two different arterioles. Consequently, six segments were analysed in each section. Special software was used to calculate percentages of positive staining in all zones in each segment. Image analysis data for each monoclonal antibody tested correlated closely with microscopical observations. The proposed strategy allows objective quantification of lymphocyte and macrophage populations and their distribution patterns. It is an useful tool for studying imbalances in cell populations in the spleen due to immune challenges.

Alterations of lymphocyte populations in lymph nodes but not in spleen during the latency period of adjuvant arthritis.

The aim of this study was to analyze potential imbalances in lymphocyte populations from regional lymph nodes (LN) and spleen occurring before the development of the outer inflammation of adjuvant arthritis (AA). Percentages and absolute numbers of CD5+, CD4+, CD8+, Ig+, I-A+, NKR-P1+ and TCRgammadelta+ cells were determined. No differences in percentages of gammadelta T or NK cells were found either in LN or spleen, thus ruling out an important role of these minor subpopulations in these early stages of AA. While no significant lymphocyte imbalances were observed in spleen, an increase in the percentage of B lymphocytes was found in regional LN. Moreover, a high proliferation of CD8+ cells was observed when measuring absolute numbers of LN lymphocytes, thus producing an imbalance in the CD4/CD8 ratio at very early stages of the inflammatory process. These findings suggest a role for CD8+ and B lymphocytes in the latency period of AA at the LN level. Our results indicate a primary role for lymph nodes in initiating the inflammation of AA, whereas cells from the spleen probably play a secondary role.

Kinetics of W3/25 anti-rat CD4 monoclonal antibody. Studies on optimal doses and time-related effects.

Although anti-CD4 monoclonal antibodies (MoAb) have been proven successful in preventing or treating adjuvant arthritis, little is known about the duration of the effects of these MoAb and their pharmacokinetics. In this work, we report the effects of a mouse anti-rat CD4 MoAb, named W3/25, on peripheral blood lymphocytes from female Wistar rats. Animals received a single dose of W3/25, from 1 to 3 mg, and blood was sampled at different time points from 0 h to 15 days after MoAb administration. After erythrocyte lysis, samples were stained by indirect immunofluorescence and analyzed by flow cytometry. Pharmacokinetic data were studied by assessing plasma levels of mouse IgG1 by ELISA-sandwich. W3/25 produced the down-regulation of surface CD4 molecule as early as 20 min after its administration at doses of 2 and 3 mg. The same effect was seen 30 min after a dose of 1 mg. The recovery of lymphocytes with normal expression of CD4 also depended of the dose administered. Thus, CD4+ lymphocytes were recovered at 48, 72 and 96 h in rats treated with 1, 2 or 3 mg of W3/25, respectively. Plasma levels of free antibody were detectable from 20 min to 72 h, 60 min to 48 h and 60 min to 24 h after administration of 3, 2 and 1 mg, respectively, of W3/25. The mouse IgG1 MoAb used in this study followed a two-compartment model and its behavior was linear.

Treatment with an anti-CD4 monoclonal antibody strongly ameliorates established rat adjuvant arthritis.

Some experimental arthritic diseases can be prevented by treatment with anti-CD4 MoAbs. Trials with ongoing disease have not been successful so far. The aim of this study was to ascertain whether W3/25 could reverse adjuvant arthritis (AA), when beginning treatment on day 14, i.e. when the disease was established. Moreover, one group of animals treated with the anti-CD4 MoAb received OX8 MoAb at the same time, thus depleting CD8+ cells from circulation. During treatment with W3/25, a strong amelioration of inflammatory signals were observed, as assessed by means of paw volume increase and arthritic score. However, when treatment stopped, a rebound to arthritis signals occurred. The parallel depletion of CD8+ cells did not modify these effects, thus the combined treatment W3/25 + OX8 gave the same amelioration as treatment with W3/25 alone. These findings indicate that CD4+ cells play an important role in perpetuating rat AA. Moreover, CD8+ cells do not seem to have a regulatory role int he CD4+ cells responsible for the inflammatory response.

Administration of a nondepleting anti-CD4 monoclonal antibody (W3/25) prevents adjuvant arthritis, even upon rechallenge: parallel administration of a depleting anti-CD8 monoclonal antibody (OX8) does not modify the effect of W3/25.

The aim of this study was to determine the effects of the anti-CD4 monoclonal antibody (mAb) W3/25, found to be nondepleting, on the onset of rat adjuvant arthritis (AA), and, in addition, to ascertain whether depletion of CD8+ cells during the same period could interfere with those effects. Female Wistar rats in which AA had been induced were treated with W3/25 and/or OX8 (anti-rat CD8) mAb during the latency period of arthritis. W3/25 alone or in combination with OX8 prevented the inflammatory process of AA. When the protected groups were rechallenged with a second dose of Mycobacterium butyricum no arthritis was observed. Protected and nonprotected arthritic animals developed the same anti-mycobacteria antibody levels as the arthritic control group. This study indicates that a nondepleting anti-CD4 mAb can prevent AA, while CD8+ lymphocytes do not appear relevant for the development of AA and do not seem to have a regulatory role for CD4+ cells.

Immunohistochemical changes in synovial tissue during the course of adjuvant arthritis.

OBJECTIVE: To study immunohistochemical changes occurring in knee synovial membranes of rats during the time course of adjuvant arthritis (AA). The effect of treatment with dexamethasone after establishment of arthritis was also studied. METHODS: AA was induced in Wistar rats by means of a single injection of a suspension of Mycobacterium butyricum. On Days 7, 14, 17, 21, 28 and 42 after induction, synovial membranes were obtained, frozen and sectioned on a cryostat. Tissue sections were tested by peroxidase-antiperoxidase method, using the following monoclonal antibodies: OX19 (CD5), W3/25 (CD4), OX8 (CD8), OX6 (Ia), OX33 (LCA) and OX39 (CD25). RESULTS: Knee synovial membranes obtained from arthritic rats on days of maximum inflammation showed few or no CD5+ cells, a higher proportion of CD8+ cells, and a higher number of CD4+ and Ia+ cells than healthy synovial tissues. CD25+ cells were observed from Day 7 postinduction and remained numerous throughout the study. CONCLUSION: Few T lymphocytes (CD5+) were found in arthritic synovial membrane, whereas an increase of cells expressing CD8, CD4, CD25, Ia, and LCA was found. These increases (except CD8) are not evident in dexamethasone treated rats.