Dermatologic and Ocular Diseases
Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172) is associated with improvement in atopic dermatitis in children with moderate-to-severe disease

https://doi.org/10.1067/mai.2001.113081Get rights and content

Abstract

Background: Although a doubling in the prevalence of atopic disease, including atopic dermatitis, in the Western world over the last few generations has been paralleled by a marked reduction in infectious diseases, especially tuberculosis, it is unclear whether this increase in atopy is causally related to reduced exposure to mycobacteria. Objectives: The aim of this study was to determine whether administration of mycobacterial antigens to atopic individuals might ameliorate their disease. Methods: Forty-one children aged 5 to 18 years with moderate-to-severe atopic dermatitis were enrolled in a randomized, double-blind, placebo-controlled trial, where they were given either one intradermal injection of killed Mycobacterium vaccae (SRL 172) or buffer solution (placebo). Changes in skin surface area affected by dermatitis and dermatitis severity score were assessed before treatment and at 1 and 3 months after treatment. Results: Children treated with SRL 172 showed a mean 48% (95% CI, 32%-65%) reduction in surface area affected by dermatitis compared with a mean 4% (95% CI, –29% to 22%) reduction for the placebo group (P < .001) and a median 68% (interquartile range, 46%-85%) reduction in dermatitis severity score compared with 18% (interquartile range, –2% to 34%) for the placebo group (P < .01) at 3 months after treatment. There were no untoward effects of the treatment, apart from a local reaction in 13 of the 21 children, which occurred 1 month after SRL 172 administration and settled spontaneously. Conclusion: SRL 172 was associated with an improvement in the severity of the dermatitis in children with moderate-to-severe disease. (J Allergy Clin Immunol 2001;107:531-4.)

Section snippets

Patients and study design

This study was conducted as a single-center, randomized, double-blind, placebo-controlled trial. The children enrolled in the study, aged 5 to 18 years, attended the University Department of Child Health outpatient clinic at Booth Hall Children’s Hospital, a regional referral center for unusually severe or persistent atopic dermatitis. Sixty children with moderate-to-severe atopic dermatitis were initially considered for the study. Eight children and their parents declined to take part, 7 were

Baseline characteristics

The baseline characteristics of the children with atopic dermatitis who took part in the study are shown in Table I.

. Baseline characteristics of subjects with atopic dermatitis randomized to placebo or SRL 172

CharacteristicPlaceboSRL 172P value
No.2021
Age (y)10 ± 49 ± 4.3
Male patients, n (%)12 (60)6 (29).04
White patients, n (%)13 (65)16 (76).4
Surface area affected (%)40 ± 3038 ± 30.8
Dermatitis score (0-300)38 (22-86)55 (19-69).8
IgE 1000 kU/mL (≤0.1)6.6 (1.7-19.7)9.2 (0.6-15.2).8
Blood eosinophil

Discussion

This randomized, double-blind, placebo-controlled study demonstrated that in the cohort of children studied, there was a significant reduction in the severity of their atopic dermatitis after a single intradermal injection of killed M vaccae suspension (SRL 172) without any major adverse effects. The lack of any placebo effect may relate to the relatively short duration of the trial and the objectivity of the assessment scores, especially the use of surface area affected by dermatitis as the

Acknowledgements

We thank Dr Leena Patel and Dr Carol Ewing for permission to use their patients in this study; Dr Kath. Bennett, CRC Paediatric and Familial Cancer Group, University of Manchester, for statistical advice; SR Pharma Ltd, London for providing SRL 172 and matching placebo; and Mrs Franscine Radavan and the pharmacy staff at Booth Hall Children’s Hospital for randomizing and allocating the treatments to the patients. Measurements of IgE levels were performed by the staff of the Department of

Cited by (156)

  • Toxocara canis extract fractions promote mainly the production of Th1 and regulatory cytokines by human leukocytes in vitro

    2022, Acta Tropica
    Citation Excerpt :

    Thus, the interaction between IL-12 and IFN-γ leads to a strong positive feedback mechanism, which is important for inflammation control mediated by the Th2 cellular immune response (Frucht et al., 2001). Indeed, inhibition of the Th2 cells accompanied by an augmentation of a Th1 cellular immune response with IFN-γ production has been reported in allergic patients following immunotherapy (Arkwright and David, 2001). Our results show that T. canis antigens activated the cytokine production of innate immunity, such as TNF-α.

  • Analysis of the immunomodulatory properties of two heat-killed mycobacterial preparations in a human whole blood model

    2015, Immunobiology
    Citation Excerpt :

    Moreover, BCG has proven to be successful in the treatment of early non-invasive bladder cancer (Kawai et al., 2013). The investigation of inactivated rapid-growing mycobacteria to be employed as immunomodulators has led to the selection of M. vaccae which was later evaluated as an immunomodulating therapeutic agent in various diseases including TB (Dlugovitzky et al., 2006; Johnson et al., 2000; Yang et al., 2011), leprosy (Abbot et al., 2002; Truoc et al., 2001), psoriasis (Lehrer et al., 1998), dermatitis (Arkwright and David 2001), asthma (Camporota et al., 2003) and a range of cancers (Cananzi et al., 2013; Eaton et al., 2002; O’Brien et al., 2004; Patel et al., 2008; Stanford et al., 2008). M. vaccae was also found to be an effective vaccine that could confer a significant level of protection against TB among HIV-infected individuals who had received BCG vaccination during childhood (von Reyn et al., 2010).

  • Mycobacteria and their world

    2012, International Journal of Mycobacteriology
  • Adjuvants and Vector Systems for Allergy Vaccines

    2011, Immunology and Allergy Clinics of North America
  • Regulatory T Cells in Infection

    2011, Advances in Immunology
  • Investigational and unproven therapies in atopic dermatitis

    2010, Immunology and Allergy Clinics of North America
View all citing articles on Scopus

Reprint requests: Peter D. Arkwright, MB, DPhil, Academic Unit of Child Health, University of Manchester, Booth Hall Children’s Hospital, Charlestown Rd, Manchester, M9 7AA, United Kingdom.

View full text