The Effect of Delipidated Deglycolipidated (DDMV) and  Heat-killed <i>Mycobacterium vaccae</i> in Asthma

Shirtcliffe, Philippa; Easthope, Stephanie E.; Cheng, Shih-Lung; Weatherall, Mark; Tan, Paul; Gros, Graham Le; Beasley, Richard

doi:10.1164/ajrccm.163.6.2003050

Cited by 58 publications

(48 citation statements)

References 6 publications

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“…The most plausible explanation for the relatively small effects in the current study may be that higher and/or more frequent doses have to be given for greater efficacy. A study by SHIRTCLIFFE et al [21], using half the dose applied in the current study and a different strain of M. vaccae (ATCC 15483), failed to reach statistical significance with regard to the number of clinical asthma outcomes.…”

Section: Discussioncontrasting

confidence: 68%

“…The timing of the challenge in relation to the injection of SRL172 was based on the attenuating effect of SRL172 in the murine ovalbumin-sensitised mouse seen 3 weeks after administration of M. vaccae [17]. However, recent evidence suggests that 3 weeks was too soon to seek maximal effect [21]. It is also possible that the immunomodulatory capacity of SRL172 varies considerably from mildly to highly allergic individuals.…”

Section: Discussionmentioning

confidence: 99%

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The effects ofMycobacterium vaccaeon allergen-induced airway responses in atopic asthma

Camporota¹,

Corkhill²,

Long³

et al. 2003

Eur Respir J

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T-helper (Th)2 cytokines play a central role in asthma. Therefore, a double-blind randomised study was conducted to investigate whether heat-killed Mycobacterium vaccae (SRL172), a potent downregulator of Th2 cytokines, can reduce allergen-induced airway responses in patients with atopic asthma.A total 24 male asthmatics participated in this study. A bronchial allergen challenge was performed along with early (EAR) and late asthmatic responses (LAR) 2 weeks before and 3 weeks after a single intradermal injection of SRL172 or placebo. Before and after treatment, serum immunoglobulin (Ig)E levels and in vitro production of interleukin (IL)-5 by peripheral blood lymphocytes were studied.Neither treatment affected the EAR. SRL172 caused a mean 34% reduction of the area under the curve of the forced expiratory volume in one second (FEV1) changes during the LAR, which failed to reach conventional statistical significance when compared with placebo. SRL172 also caused a mean 25% decrease in the maximum fall in FEV1 during LAR, but this was not significantly different from placebo. SRL172 caused a reduction in serum IgE and IL-5 synthesis in vitro 3 weeks post-treatment (p=0.07).This study shows a trend toward significance for the effects of heat-killed Mycobacterium vaccae (SRL172) on allergen-induced airway responses. Further clinical trials, involving multiple dosing, are needed.

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Section: Discussioncontrasting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

The effects ofMycobacterium vaccaeon allergen-induced airway responses in atopic asthma

Camporota¹,

Corkhill²,

Long³

et al. 2003

Eur Respir J

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“…This work has drawn on widespread acceptance of the hygiene hypothesis, which is a well recognised, if oversimplified, link between infection and allergy. Administration of mycobacteria and other Th1-inducing infectious agents for the treatment of asthma in humans has given disappointing results, and successful results were dependent on the age of study subjects [4,12,14]. The therapeutic use of S. pneumoniae antigens that may prevent Th2 and eosinophil development and mobilisation by a different mechanism, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Administration of mycobacterial components inhibits allergic airway disease (AAD); however, the efficacy of mycobacterial treatment in preventing allergic diseases in human trials has been varied, with decreases in the severity of atopic dermatitis but no affect on allergic asthma [11][12][13].…”

mentioning

confidence: 99%

Streptococcus pneumoniaeinfection suppresses allergic airways disease by inducing regulatory T-cells

Preston¹,

Thorburn²,

Starkey³

et al. 2010

Eur Respir J

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An inverse association exists between some bacterial infections and the prevalence of asthma. We investigated whether Streptococcus pneumoniae infection protects against asthma using mouse models of ovalbumin (OVA)-induced allergic airway disease (AAD).Mice were intratracheally infected or treated with killed S. pneumoniae before, during or after OVA sensitisation and subsequent challenge. The effects of S. pneumoniae on AAD were assessed.Infection or treatment with killed S. pneumoniae suppressed hallmark features of AAD, including antigen-specific T-helper cell (Th) type 2 cytokine and antibody responses, peripheral and pulmonary eosinophil accumulation, goblet cell hyperplasia, and airway hyperresponsiveness. The effect of infection on the development of specific features of AAD depended on the timing of infection relative to allergic sensitisation and challenge. Infection induced significant increases in regulatory T-cell (Treg) numbers in lymph nodes, which correlated with the degree of suppression of AAD. Tregs reduced T-cell proliferation and Th2 cytokine release. The suppressive effects of infection were reversed by anti-CD25 treatment.Respiratory infection or treatment with S. pneumoniae attenuates allergic immune responses and suppresses AAD. These effects may be mediated by S. pneumoniae-induced Tregs. This identifies the potential for the development of therapeutic agents for asthma from S. pneumoniae.

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“…]). Studies using BCG [51] or heat-killed M. vaccae [52] therapeutically in established asthma or atopic dermatitis [53], however, showed beneficial effects of mycobacterial treatment, although the effect of M. vaccae in asthma patients was not confirmed [54]. These contrasting results might be explained by the fact that a lot of variables were different in these studies, such as the age at and the frequency of vaccination with mycobacteria, the BCG strain used and the varying natural exposure to mycobacteria (including M. tuberculosis) or allergens [55].…”

Section: Mycobacteria and Allergy In Humansmentioning

confidence: 99%

Mycobacteria, genes and the ‘hygiene hypothesis’

Smit

Folkerts

Nijkamp

2004

Current Opinion in Allergy and Clinical Immunology

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Purpose of reviewThe 'hygiene hypothesis' suggests that a relationship exists between improved hygiene and an increase in allergic diseases. As an underlying mechanism for this hypothesis it is proposed that due to the lack of microbial stimulation either a misbalance in T helper type responses or a misbalance in regulatory mechanisms develops. As yet, however, a specific infectious factor responsible for the hygiene hypothesis has not been found. Recent findingsAnimal models have lent support for mycobacteria as important candidates in the hygiene hypothesis. These animal studies have also suggested that mycobacterial treatment generated regulatory mechanisms which restored the immune balance. In contrast, the relationship between mycobacterial infection or treatment and the development of allergy and asthma in humans is unclear and highly controversial. Summary Mycobacteria have been found to unambiguously reduce allergic and asthmatic manifestations, suggesting that mycobacteria perhaps can be used as an 'anti-asthma' vaccine. Conflicting results in humans, however, confirm that the complex and multifactorial interactions between the environment and the genetic background of the individual contribute to the development of allergic disease. Therefore, the hygiene hypothesis should involve the genetic and the environmental background of the individual.

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The Effect of Delipidated Deglycolipidated (DDMV) and Heat-killed Mycobacterium vaccae in Asthma

Cited by 58 publications

References 6 publications

The effects ofMycobacterium vaccaeon allergen-induced airway responses in atopic asthma

The effects ofMycobacterium vaccaeon allergen-induced airway responses in atopic asthma

Streptococcus pneumoniaeinfection suppresses allergic airways disease by inducing regulatory T-cells

Mycobacteria, genes and the ‘hygiene hypothesis’

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