Bovine milk fat enriched in conjugated linoleic and vaccenic acids attenuates allergic airway disease in mice.

BACKGROUND: It has been argued that a reduction in the Western diet of anti-inflammatory unsaturated lipids, such as n-3 polyunsaturated fatty acids, has contributed to the increase in the frequency and severity of allergic diseases. OBJECTIVE: We investigated whether feeding milk fat enriched in conjugated linoleic acid and vaccenic acids (VAs) ('enriched' milk fat), produced by supplementing the diet of pasture-fed cows with fish and sunflower oil, will prevent development of allergic airway responses. METHODS: C57BL/6 mice were fed a control diet containing soybean oil and diets supplemented with milk lipids. They were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 14 and 28, and challenged intranasally with OVA on day 42. Bronchoalveolar lavage fluid, lung tissues and serum samples were collected 6 days after the intranasal challenge. RESULTS: Feeding of enriched milk fat led to marked suppression of airway inflammation as evidenced by reductions in eosinophilia and lymphocytosis in the airways, compared with feeding of normal milk fat and control diet. Enriched milk fat significantly reduced circulating allergen-specific IgE and IgG1 levels, together with reductions in bronchoalveolar lavage fluid of IL-5 and CCL11. Treatment significantly inhibited changes in the airway including airway epithelial cell hypertrophy, goblet cell metaplasia and mucus hypersecretion. The two major components of enriched milk fat, cis-9, trans-11 conjugated linoleic acid and VA, inhibited airway inflammation when fed together to mice, whereas alone they were not effective. CONCLUSION: Milk fat enriched in conjugated linoleic and VAs suppresses inflammation and changes to the airways in an animal model of allergic airway disease.

Pilot study investigating the ability of an herbal composite to alleviate clinical signs of respiratory dysfunction in horses with recurrent airway obstruction.

Recurrent airway obstruction (RAO), known previously as chronic obstructive pulmonary disease (COPD), is a debilitating respiratory condition that significantly contributes to lost training days and illness in racehorses. Herbs are becoming increasingly popular for the prophylaxis or treatment of the clinical signs of RAO despite a paucity of research on efficacy and safety. We evaluated the ability of an herbal composite containing garlic, white horehound, boneset, aniseed, fennel, licorice, thyme, and hyssop to reduce the clinical signs of RAO, hypothesizing that the product would safely reduce signs and would improve the inflammatory cell profile within the lungs. The composite was fed to 6 horses with symptomatic RAO for 21 d in a crossover manner. Ventigraphs were used to record respiratory rate and intrapleural pressure; the proportion of inflammatory cells in fluid aspirated from the trachea was determined. Blood biochemical and hematologic screening was conducted to identify possible adverse effects. Treatment with the composite did not result in statistically significant changes in any of the parameters evaluated. A trend to a decrease in respiratory rate (P = 0.1) and an increase in the proportion of macrophages (P = 0.1) was observed in the horses receiving the herbal composite compared with placebo. These data indicate a potential for the herbal composite to safely reduce the elevated respiratory rate in horses with RAO. Future research with a greater number of horses is warranted to further characterize the effect of this product on horses with RAO.

Inhibitors of mitogen-activated protein kinases differentially regulate eosinophil-activating cytokine release from human airway smooth muscle.

Airway smooth muscle (ASM) is a potential source of multiple proinflammatory cytokines during airway inflammation. In the present study, we examined a requirement for mitogen-activated protein (MAP) kinase activation for interleukin (IL)-1beta-stimulated GM-CSF, RANTES, and eotaxin release. IL-1beta induced concentration-dependent phosphorylation of p42/p44 extracellular signal-regulated kinases (ERKs), p38 MAP kinase, and c-Jun amino-terminal kinase (SAPK/JNK). p42/p44 ERK and p38 MAP kinase phosphorylation peaked at 15 min and remained elevated up to 4 h. SAPK/JNK phosphorylation also peaked at 15 min but fell to baseline within 60 min. SB 203580 selectively inhibited IL-1beta-stimulated activation of p38 MAP kinase; U 0126 was selective against p42/p44 ERK activity. SB 202474, an inactive analog, had no effect on p42/p44 ERK, p38 MAP kinase, or SAPK/JNK activation, or on eotaxin or RANTES release. Eotaxin release was inhibited by SB 203580 and U 0126, whereas RANTES release was prevented by U 0126 only. GM-CSF release was inhibited by U 0126 but enhanced by SB 203580. These data indicate that RANTES release is dependent on p42/p44 ERK activation but occurs independently of p38 MAP kinase activity. Eotaxin release, however, is dependent on both p38 MAP kinase- and p42/p44 ERK-dependent mechanisms. GM-CSF release is p42/p44 ERK dependent and is tonically suppressed by a mechanism that is partially dependent on p38 MAP kinase, though direct inhibition of cyclooxygenase (COX) activity due to poor inhibitor selectivity may also contribute.

Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (inmunoferón).

We have investigated both modifications in natural (innate) immunity caused by chronic obstructive pulmonary disease (COPD) and the effects of a glycophosphopeptical immunomodulator (Inmunoferón) treatment on COPD-associated immunoalterations. In a double-blinded clinical trial, 60 patients with COPD received glycophosphopeptical or placebo during 90 consecutive days at oral doses of 3 g/d. Fifty-six sex- and age-matched healthy control subjects were included as a reference group for immunologic parameters. Peripheral blood natural killer (PBNK) cell cytotoxic activity and phagocytic activity of peripheral monocytes/macrophages (Mo/Ma) and polymorphonuclear (PMN) cells were assessed at baseline and then again at the end of treatments. We found both PBNK activity and phagocytic activity to be significantly decreased in patients with COPD compared with levels in healthy volunteers. The treatment with glycophosphopeptical provoked significant stimulatory effects on PBNK cytotoxic activity. This stimulation was not mediated by an increase in CD3(-)CD56(+) NK cells. Further, glycophosphopeptical significantly increased the percentage of monocytes and PMNs that phagocytize Escherichia coli in vitro, as well as increased phagocytic indices. We conclude that peripheral blood cells of patients with COPD show clear defects in natural immunity that are partially rescued by glycophosphopeptical.

IL-10 reduces grain dust-induced airway inflammation and airway hyperreactivity.

To determine whether interleukin-10 (IL-10) could alter the development of grain dust-induced airway disease, we pretreated mice with either saline or IL-10 intravenously, exposed the mice to an inhalation challenge with corn dust extract (CDE), and measured inflammation and the development of airway hyperreactivity. Pretreatment with IL-10, in comparison to saline, reduced the concentration and percentage of polymorphonuclear cells in the lavage fluid 30 min after the inhalation challenge with CDE (P < 0. 05). In comparison to saline-treated mice, IL-10 did not significantly alter the degree of airway hyperreactivity 30 min after the exposure to CDE. IL-10-treated mice lavaged 18 h after challenge with CDE also exhibited a lower percentage of polymorphonuclear cells in the lavage fluid (P < 0.05) and had significantly less airway hyperreactivity than did mice pretreated with the saline placebo (P < 0.05). These findings indicate that exogenous IL-10 is effective in reducing airway inflammation and airway hyperreactivity due to the inhalation of CDE.

[An intensive regimen of pelotherapy in pulmonology]. / Intensivnyi rezhim peloidoterapii v pul'monologii.

The authors show that intensification of peloid therapy, i.e. more frequent procedures, in patients with pulmonary diseases imposes additional load on the regulatory systems: vegetative, cardiovascular, immune. Moderate balneological reactions become more frequent, therapeutic results worsen. How to correct the above negative effects is proposed.

[The effects of small dosage inactivated BCG vaccine on cellular immune function of pulmonary chronic obstructive disease patients with deficiency of lung-qi].

UNLABELLED: To investigate the effects of the small dosage inactivated BCG vaccine on the cellular immune function of the patients suffered from pulmonary chronic obstructive disease with deficiency of the Lung-Qi, the authors observed the patients' immune function before and after BCG treatment for half a year. RESULTS: The peripheral blood T lymphocytes subsefs (CD3, CD4, CD8, CD4/CD8) and the conversion ratio of lymphocyte of the patients both were significantly lower than those of the healthy people (P < 0.01). But after the treatment of the small dosage inactivated BCG vaccine for half a year, these parameters of the patients were improved (P < 0.01 or P < 0.05). It indicated that the small dosage inactivated BCG vaccine could improve the damaged cellular immune function.

[Clinical observation of Qi deficiency syndrome in 72 patients with chronic obstructive pulmonary disease treated with yiqi mianyi granule].

Seventy-two patients of chronic obstructive pulmonary disease (COPD) of Qi deficiency syndrome with abnormal immune indices were treated with Yiqi Mianyi Granule (YQMYG) and the efficacy was compared with 30 cases treated with Zhenqi Fuzheng Granule (ZQFZG) for control. Results showed that the marked effective rate of symptomatic improvement of Qi Deficiency in YQMYG group was 65.3%, the total effective rate was 93.1%. 88.6% of the immune indices lower than normal were corrected and 43.7% of them were normalized, while for indices higher than normal the rate were 78.2% and 52.9% respectively. These results suggested that YQMYG could improve the symptom of Qi Deficiency markedly, strengthen the cellular immunity, regulate the disorder of immune function, its therapeutic efficacy was obviously superior to ZQFZG (P < 0.05).

Ex vivo evaluation of pidotimod activity in patients with chronic obstructive pulmonary disease.

The aim of this study was to evaluate the activity of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) on 52 patients affected with chronic obstructive pulmonary disease (COPD). The study was carried out in a randomized, parallel, double-blind trial, followed by incomplete blocks design. Pidotimod 800 mg was administered orally twice a day for 30 days. The follow-up period was 5 weeks. Our results show that in patients with COPD pidotimod potentiates T-cell activity. The effects on T-cells appear after 15 days of treatment and last for 5 weeks after the end of therapy. Since other studies demonstrated that pidotimod displays an immunopotentiating activity also on macrophages and granulocytes, the drug is useful to increase the immune defense during infections. The drug has a good compliance and is well tolerated also during long-term treatment.

[The immunological rehabilitation of patients with chronic nonspecific lung diseases at sanatoria and health resorts]. / Immunoreabilitatsiia bol'nykh khronicheskimi nespetsificheskimi zabolevaniiami legkikh v sanatorno-kurortnykh usloviiakh.

Basing on the data obtained from a comparative study of hypoxia-hypercapnia training according to "return" respiration versus an apilactose course in patients treated in sanatoria for chronic nonspecific pulmonary diseases, the authors developed an effective complex correcting local, systemic immunity and hormonal levels.

[Effect of electromagnetic EUHF-radiation of non-thermal intensity on the function of the respiratory and cardiovascular system and some parameters of the cell immunity in respiratory pathology]. / Vliianie élektromagnitnykh KSVCh-izluchenii neteplovoi intensivnosti na funktsiiu dykhatel'noi i serdechno-sosudistoi sistem i nekotorye pokazateli kletochnogo immuniteta pri patologii organov dykhaniia.

The electromagnetic radiation of mm-range and 3 mW/cm2-flow density has been studied for its effect on the function of the respiratory-hemodynamic system in some parameters of the cell immunity and on the sensory sphere of patients with chronic obstructive diseases of the lungs. The therapeutic exposure was performed by the method of cascade EUHF-reflexotherapy. It is shown that such a radiation promotes stabilization of the chronic broncho-obstructive process. The exposure features revealed allow recommending the cascade EUHF-reflexotherapy for a routine use in the complex rehabilitation of patients with chronic obstructive diseases of the lungs.

[Changes in the clinico-functional and immunological indices of patients with chronic obstructive lung disease, the allergic form, following combined climatotherapy at Sandanski health resort]. / Promeni v niakoi kliniko-funktsionalni i imunologichni pokazateli pri bolni s khronichna obstruktivna belodrobna bolest--alergichna forma, sled kompleksno klimatolechenie v kurorta Sandanski.

20 patients with chronic obstructive pulmonary disease who were treated in the resort of Sandanski, Bulgaria, during the autumn of 1988 were investigated for changes of some clinical, functional and immunologic indices--secretory immunoglobulins, lysozyme, serum bactericidal activity. The results revealed an improvement of the clinical indices mean in 50% of the patients, of the expiratory spirometric indices in mean 47% of the patients. Other findings were a distinct tendency towards a decrease of IgG and albumin in the saliva and an increase of the secretory IgA together with a statistically significant increase of the indices characterizing the nonspecific defence mechanisms of the lung.

On the problem of nonsense correlations in allergological tests after routine extraction.

The influence of extraction procedures and culturing methods of material used for the preparation of allergenic extracts on correlation patterns found in allergological testing (skin test and RAST) was investigated. In our laboratory a short extraction procedure performed at O degrees C was used for Aspergillus repens. A. penicilloides, Wallemia sebi, their rearing media and non-inoculated medium. For the commercially available extracts from house dust, house-dust mite, pollen of Dactylus glomerata and A. penicilloides a longer procedure (several days) performed at room temperature was used. Statistical analysis showed a separation of all test results into two clusters, each cluster being composed of correlations between extracts from only one the manufacturers did not show any correlation. The correlations found between the short time incubated extracts of the xerophilic fungi and their rearing media could be explained by genetical and biochemical relationships between these fungi depending on ecological conditions. However, while the correlation found between house dust and house-dust mite is understandable, correlations found between long time incubated extracts from house-dust mite and D. glomerata or A. penicilloides may be nonsense correlations, that do not adequately describe the in vivo situation. The similarity of these extracts is presumably artificially created during extraction.

Quantitation of proteins in sputum from patients with chronic obstructive lung disease. I. Determination of immunoglobulin A.

Samples of sputum from nine patients with chronic obstructive lung disease were collected every morning for 5 consecutive days, and their mean apparent viscosities were determined. After a standard solubilization procedure, the concentration of immunoglobulin A (IgA) in each sample was determined by quantitative immunodiffusion and also by an immunofluorimetric method, using dimeric IgA purified from colostrum as a standard. The two methods gave diverging results probably reflecting different sensitivities of the techniques to various classes of IgA (monomers, dimers and polymers). The concentration of IgA was found to vary from 1.2 to 3.9 g/l with a mean value of 2.3 g/l for the 45 samples using the immunodiffusion technique, and from 1.3 to 4.9 g/l with a mean value of 3.5 g/l using the immunofluorimetric method. In agreement with earlier observations, a weak correlation was shown between the concentration of IgA in the samples and their mean viscosities. A similar correlation was, however, demonstrated between IgA and the total content of protein in the soluble part of the samples. It could therefore not be decided whether IgA itself or other proteins in the sputa were responsible for the observed effect on viscosity.

Chronic obstructive pulmonary disease (COPD) in horses: aetiological studies: responses to intradermal and inhalation antigenic challenge.

Micropolyspora faeni and Aspergillus fumigatus were identified as common causes of respiratory hypersensitivity in horses affected with chronic obstructive pulmonary disease (COPD). Rye grass pollen and an Actinomycete evoked respiratory allergy in a few horses. Not infrequently, individual horses were found to have respiratory hypersensitivity to two or more antigens. The methods used to examine for allergy were intradermal testing and inhalation challenge with environmental antigens. An intradermal test using an M faeni extract was demonstrated to be suitable for diagnostic use in horses previously accurately diagnosed as suffering from COPD. In contrast, the A fumigatus antigen used proved unsatisfactory for such a purpose. Skin reaction to M faeni and A fumigatus extracts by horses affected with COPD indicated that the hypersensitivity was a dual one--a weak response shortly after injection followed by an Arthus-like response 4 to 8 hours later. As a parameter for monitoring responses to inhalation challenge, maximum intrathoracic pressure change (max delta Ppl) proved satisfactory, whereas changes in partial pressure of arterial oxygen (PaO2) did not.