Disodium cromoglycate may act as a novel adjuvant for UV-attenuated Toxoplasma gondii vaccine in mouse model.

We have proven the beneficial effects during acute Toxoplasma gondii infection when mast cells were inhibited by disodium cromoglycate (DSCG). Here we investigated the adjuvant effect of DSCG on the protective efficacy of UV-attenuated T. gondii (UV-Tg) vaccine. Mice were infected with 102Tg alone or infected with 102Tg plus DSCG (Tg + DSCG), immunized with 105 UV-Tg and challenged with 102Tg (UV-Tg + Tg) or immunized with 105 UV-Tg plus DSCG and challenged with 102Tg (UV-Tg + DSCG + Tg). Compared to Tg group, Tg + DSCG, UV-Tg + Tg, and UV-Tg + DSCG + Tg showed significantly prolonged survival times, decreased parasite burdens, reduced liver histopathologies, and increased levels of Th1 and Th2 cytokines and IL-17 in the livers and spleens by using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Compared to UV-Tg + Tg, UV-Tg + DSCG + Tg had significantly longer survival time, lower tissue parasite burden and histopathological score, and higher levels of Th1 and Th2 cytokines and IL-17 in the livers or spleens. Our data suggest that DSCG may play an adjuvant role in the immunization induced by UV-attenuated T. gondii in mice, by promoting cellular immune response against T. gondii challenge.

DSCG reduces RSV-induced illness in RSV-infected mice.

Respiratory syncytial virus (RSV) is one of the pathogens generally associated with the common cold, lower respiratory infection, and exacerbation of asthma. Disodium cromoglycate (DSCG) is a safe and widely used drug for the prevention of bronchial asthma and allergic rhinitis attacks. The effect of DSCG on acute upper respiratory tract viral infections remains controversial. The purpose of the study was to investigate the effects of DSCG on parameters of RSV induced-illness. Using a well-characterized murine model of RSV infection, the effect of DSCG on RSV-induced illness was evaluated by body weight, respiratory function, viral replication, level of IFN-gamma in lungs, serology, and histopathology. Mice treated with DSCG were protected against RSV-induced weight loss. The baseline Penh in RSV-infected mice treated with DSCG was less than that in mice treated with saline. In methacholine challenge, the increase in Penh in RSV-infected mice treated with DSCG was suppressed to the same level as that in the mock-infected group. Further, there were no differences in viral replication between the mice treated with DSCG and those treated with saline, and the level of inflammation observed in the lungs in RSV-infected mice treated with DSCG was not as severe as that in mice treated with saline. These findings indicate that DSCG may be an effective agent for the prevention of RSV induced disease and the relief of symptoms of RSV infection.

Perinatal immunomodulation.

The fetus and the neonate are particularly vulnerable to injury caused directly by immunologic mechanisms or inflicted by infectious agents that take advantage of their relatively immature and inexperienced immune system. With increasing survival of high-risk neonates in the surfactant era, prevention/treatment of sepsis and chronic lung disease (CLD) has emerged as an area of priority in neonatal research. Considering the role of inflammatory mediators in the pathogenesis of sepsis and CLD, the clinical application of immunomodulator therapy to neonatology is perhaps more important at present than ever. Advances in molecular biology and immunology have led to development of newer immune modulator therapies that are directed towards specific cells or cytokines rather than resulting in a general suppression of the immune response. Failure of promising, newer immunomodulator therapies in sepsis trials in adults has, however, clearly documented the difficulties in diagnosing/correcting the imbalance between pro- and anti-inflammatory responses. As in the case of sepsis, development of a single magic bullet for prevention/management of a multi-factorial illness like CLD may be difficult, as prevention of prematurity - the single most important high-risk factor for CLD - is an unachievable goal at present. As new frontiers are being explored, older, well-established therapies like antenatal anti-D immunoglobulin prophylaxis continue to emphasize the tremendous potential of immunomodulator therapy in neonatology/perinatology. The current immunomodulators/immunotherapeutic agents with established/potential clinical applications in the perinatal period are reviewed.

Severe allergic conjunctivitis and chemosis caused by disodium cromoglycate.

A 63-year-old man with chronic, nonallergic rhinoconjunctivitis presented immediate adverse reactions, such as intense itching, burning, redness and severe swelling of both conjunctivae after using disodium cromoglycate eye drops. Skin prick tests and conjunctival provocation tests were positive with pure disodium cromoglycate. Circulating IgE-specific antibodies to disodium cromoglycate in serum were demonstrated by RAST. We suggest that the acute ocular reaction was caused by disodium cromoglycate and that the underlying mechanism was probably an IgE-mediated immunological reaction.

Efecto in vitro del cromoglicato disódico sobre la actividad fagocítica de los polimorfonucleares de pacientes asmáticos sanos / Disodium chromoglicate reduces in vitro phogcytic activity of the polymorphonuclear cells in asthmatic patients and healthy

El cromoglicato disódico (CGDS) interfiere con el trasporte de la membrana celular inhibiendo la liberación de mediadores y la activación de polimorfonucleares (PMN), al impedir el incremento del calcio libre intracelular. Para determinar si el CGDS disminuye la actividad fagocítica in vitro de PMN se incubaron PMN de personas sanas y asmáticos alérgicos con CGDS o con solución salina balanceada de Hank (SSBH) y se evaluó su actividad fagocítica con la técnica de quimioluminiscencia. Al comparar las muestras no se encontró diferencia significativa con la actividad fagocítica entre las incubadas con CGDS y las incubadas en SSBH sin CGDS; tampoco se halló diferencia en la actividad fagocítica entre los asmáticos y sanos y no hay diferencia en la capacidad fagocítica de PMN entre asmáticos y sanos

Evaluación clínica del cromoglicato de sodio en solución nasal al 2 por ciento en el tratamiento de la rinitis alérgica / Clinic evaluation of the 2 per cent cromoglycate sodium chomoglycate nasal solution in the allergic rhinitis

Resultados de un estudio doble ciego donde 30 pacientes con síntomas de rinitis alérgica y edades de 6 a 50 años fueron asignados aleatoriamente para recibir solución activa con CGS al 2 por ciento, un disparo en cada narina cada seis horas o solución con placebo. Todos los individuos recibieron astemizol 10 mg en ayunas diariamente e hiposensibilización durante un periodo de seis meses a dos años. Se revisaron los diarios en donde se anotaban los síntomas de los pacientes cada dos semanas durante siete visitas y se les efectuó exploración física. Ambos grupos tuvieron promedio de agudización de síntomas de rinitis comparable al inicio del estudio. Después de 45 días de tratamiento y en el seguimiento a tres meses, los promedios de síntomas indicaron superioridad del CGS en solución nasal para reducir la gravedad de la rinorrea, obstrucción nasal y estornudos; así como disminución de la secreción nasal y edema de cornetes (p<0.001). Los pacientes con CGS mejoraron significativamente según la valoración global hecha por el investigador (p<0.05). No hubo efectos secundarios en ninguno de los grupos

Sodium cromoglycate: a review.

Sodium cromoglycate is a drug widely used in the treatment of bronchial asthma. In vitro and animal models show that its effect is related to mast cell stabilization and to a direct action on inflammatory cells or the broncho-obstructive reflex. In man, sodium cromoglycate is able to prevent bronchoconstriction induced by a variety of stimuli including the 'late' reaction to allergen. It is also able to prevent the allergen-induced increase in hyperresponsiveness. Long-term therapeutic trials have confirmed its validity in the treatment of asthmatic patients.

[A case of bronchial asthma and PIE Syndrome induced by disodium cromoglycate].

A 54-year-old female with bronchial asthma and PIE syndrome induced by disodium cromoglycate (DSCG) was reported. She was referred to our hospital for further examination of the abnormal chest shadows and eosinophilia. She had been treated with DSCG, Cefaclor. Bromhexine and bronchodilator for bronchial asthma and bronchitis. Withdrawal of the drugs except for the bronchodilators alleviated her symptoms. Therefore, drug induced lymphocytes stimulation tests (DLST) were performed for those three drugs. Only DLST for DSCG showed a positive result. She had been asthmatic for ten years and treated by the drug for 18 months prior to admission. The skin test for the drug was negative and a precipitating antibody for the drug could not be found. To obtain a definite diagnosis, bronchial challenge by DSCG was performed, after her symptoms were under control. Severe asthmatic responses were provoked in 6 and 24 hours after the inhalation of DSCG. Bronchoalveolar lavage, performed 8 days after the provocation, revealed increased eosinophils and lymphocytes in BAL fluid. Although several cases of PIE syndrome induced by DSCG have been reported, this seems to be the first report of late and delayed type bronchial response and pulmonary infiltration with eosinophilia provoked by DSCG. The bronchial response to the drug was a late and delayed type reaction and sustained for a long period. This might indicate that PIE syndrome induced by the drug may be caused by a same mechanism as the provoked asthmatic response.

Assay of specific IgE antibodies to disodium cromoglycate in serum from a patient with an immediate hypersensitivity reaction.

A 29-year-old man with pollen allergy had experienced immediate adverse reactions, such as itching of the eyes, rhinitis, wheezing, and general urticaria, after using disodium cromoglycate (DSCG) eye drops. The local symptoms were reproducible, and skin tests were strongly positive. With serum from the patient, a RAST was developed for the assay of IgE antibodies. The uptake on RAST disks was 6% of the total activity added, which was a significantly higher level than was found in sera from 35 randomly selected blood donors or in sera from 25 patients tolerating DSCG. By addition of DSCG to the patient's serum, 95% of the binding to paper disks could be inhibited. The induction of specific IgE antibodies was proposed to be a result of a combination of electrostatic and hydrophobic interaction of DSCG and a protein carrier. The substance would thus act as a hapten without any covalent binding to the carrier. DSCG may serve as a model for other nonreactive low-molecular-weight substances suspected to elicit type I-like adverse reactions.

The topical effects of Wy-41,195 [2-cyano-3-(methylamino)phenylamino] oxoacetic acid, sodium salt and disodium cromoglycate in the rat passive eyelid anaphylaxis.

Wy-41,195 demonstrated significant inhibitory effects (54-60%) when administered topically at 0.25-2% concentrations in a rat passive eyelid anaphylaxis assay. In contrast, topically applied disodium cromoglycate (DSCG) showed non significant inhibition at these concentrations. The potency of Wy-41,195 was more than 8 times greater than DSCG, and this compound may be an effective topical agent in man in preventing allergic and associated conditions.

The anti-allergic effects of FPL 52694.

The substituted chromone carboxylic acid FPL 52694 inhibited models of IgE-mediated immediate hypersensitivity reactions in the rat by a mechanism similar to that of sodium cromoglycate. The compound was more potent than sodium cromoglycate but unlike cromoglycate was active following oral administration.

The effect of disodium cromoglycate on in vitro mast cell degranulation in human jejunal mucosa.

The in vitro effect of disodium cromoglycate (DSCG) on IgE antigen-induced mast cell degranulation is described. Serum from an egg white allergic patient was used to sensitize jejunal mucosa from nine individuals. Egg white was used to challenge the IgE sensitized mast cells. DSCG in concentrations 3 x 10(-7) M to 3 x 10(-4) M was added to the mucosal specimens before antigen challenge. Mast cell degranulation in the sensitized specimens challenged with egg white was 38%. Mast cell degranulation in sensitized specimens treated with DSCG before and during antigen challenge was reduced to 2% at a concentration of 3 x 10(-5) M of DSCG (P=0.006) and to 28% at a concentration of 3 x 10(-6) M (P=0.027). No significant reduction of mast cell degranulation was seen at concentrations of 3 x 10(-7) M and 3 x 10(-4) M. The results support a role for DSCG in the treatment of gastrointestinal allergy.

Immunologic components of hypersensitivity reactions to cromolyn sodium.

Manifestations of cellular and humoral hypersensitivity to cromolyn sodium were sought in six asthmatic patients suspected of having acute (three cases) or subacute (three cases) adverse reactions to cromolyn inhalation. Lymphocytes from all patients produced migration inhibition factor (MIF), and those from four patients incorporated increased amounts of 3H-thymidine in response to cromolyn in vitro. Lymphocytes from four of nine cromolyn-tolerant asthmatics demonstrated increased 3H-thymidine incorporation but none showed MIF production, whereas lymphocytes from normal subjects failed to react to cromolyn in either assay. Two of three patients with subacute reactions had increased serum binding of 3H-cromoglycate which was attributable to the IgG fraction. Thus although patients tolerating cromolyn therapy may demonstrate lymphocyte transformation in vitro, only those with clinically apparent adverse reactions produce lymphocyte MIF or possess serum-binding activity for the drug.