Prudence Hart

Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study

Vitamin D has been linked in some studies with atopy- and asthma-associated phenotypes in children with established disease, but its role in disease inception at the community level is less clear. The aim of the present study was to investigate associations between vitamin D status and biological signatures indicative of allergy and asthma development in children aged 6 and 14 years in Perth, WA, Australia (latitude 32° S). Serum vitamin D was assayed in 989 6-yr-olds and 1,380 14-yr-olds from an unselected community birth cohort; 689 subjects were assessed at both ages. Vitamin D levels were assessed as a risk modifier for respiratory and allergic outcomes at both ages, using previously ascertained phenotypic data. The predictive value of vitamin D levels at age 6 yrs for development of clinical phenotypes at age 14 yrs was also examined. Serum vitamin D levels in children of both ages were negatively associated with concurrent allergic phenotypes; sex stratification revealed that this association was restricted mainly to males. Furthermore, vitamin D levels at age 6 yrs were significant predictors of subsequent atopy/asthma-associated phenotypes at age 14 yrs. In an unselected community setting, children (particularly males) with inadequate vitamin D are at increased risk of developing atopy, and subsequently bronchial hyperresponsiveness (BHR) and asthma. In a large unselected cohort, males with inadequate vitamin D at 6 and 14 yrs of age had increased atopy and BHR. Low vitamin D at age 6 yrs was a predictor of atopy and asthma at 14 yrs of age.

Suppression of the asthmatic phenotype by ultraviolet B-induced, antigen-specific regulatory cells

Background Over recent decades, there has been a significant global increase in the prevalence of asthma, an inflammatory disease of the respiratory system. While ultraviolet radiation (UV) has been used successfully in the treatment of inflammatory conditions such as psoriasis, studies of UV‐induced regulation of allergic respiratory responses have been rare, and have not analysed in vivo measurements of airway hyperresponsiveness (AHR) or the antigen specificity of the UV‐induced effects.

Reduction of nickel-induced contact hypersensitivity reactions by topical tea tree oil in humans.

Abstract.Objective and Design: Whilst the anti-microbial properties of tea tree oil (TTO) are established, the anti-inflammatory effects of TTO in human skin remain largely anecdotal and require evaluation. This study examined the effect of topically applied TTO on nickel-induced contact hypersensitivity reactions in human dorsal skin.Treatment: TTO (100%), a 5% TTO lotion, a placebo lotion (no TTO), or 100% macadamia oil were applied at days 3 and 5 after nickel exposure.Methods: The flare area and erythema index were measured on days 3, 5 and 7. The regulatory effects of TTO were also investigated on the proliferative response to nickel or polyclonal mitogens by peripheral blood mononuclear cells from nickel-sensitive and control subjects.Results: TTO (100%) significantly reduced the flare area and erythema index when compared to the nickel-only sites. With respect to the erythema index, the anti-inflammatory effects were predominantly, but not exclusively, seen in a subgroup of nickel-sensitive subjects with a prolonged development phase of nickel-induced contact hypersensitivity response. The 5% TTO lotion, the placebo lotion and the 100% macadamia oil were all without significant effect. TTO significantly inhibited proliferation to nickel but not to non-specific polyclonal mitogens by peripheral blood mononuclear cells from nickel-sensitive subjects.Conclusions: Topical application of 100% TTO may have therapeutic benefit in nickel-induced contact hypersensitivity in human skin. The mode of action of TTO requires further investigation, but may be an effect on the antigen presenting cells or the antigen presenting process in nickel-induced contact hypersensitivity, as well as vascular changes associated with this response.

UV inhibits allergic airways disease in mice by reducing effector CD4 T cells.

Background In human asthma, and experimental allergic airways disease in mice, antigen‐presenting cells and CD4+ effector cells at the airway mucosa orchestrate, and CD4+CD25+ regulatory T cells attenuate, allergen immunity. UV irradiation of skin before sensitization with ovalbumin (OVA) causes significantly reduced asthma‐like responses in respiratory tissues.

The controversial role of vitamin D in the skin: immunosuppression vs. photoprotection

Vitamin D is produced in the skin by ultraviolet (UV) B radiation (290–320 nm). The active metabolite 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] is made systemically by hydroxylation of vitamin D in the liver and the kidney, but also locally in the epidermis, which suggests that 1,25(OH)2D3 may have important functions in the skin. 1,25(OH)2D3 has opposing effects: it can mimic immunosuppressive effects caused by UV irradiation in some models, or reverse UV‐induced DNA damage and immunosuppression in other models. 1,25(OH)2D3 exerts effects on Langerhans cells that are characteristic of those associated with UV radiation (UVR)‐induced suppression of contact hypersensitivity, and topical application of the vitamin D analogue calcipotriene suppresses contact hypersensitivity in human subjects to a similar extent as UVR. However, 1,25(OH)2D3 decreases DNA damage both in vitro when added to human skin cells in culture before and after UVR, and in vivo when applied to mouse skin after UVR. Furthermore, topical 1,25(OH)2D3 applied to mouse skin after UVR reversed the immunosuppressive effect of UVR in a contact hypersensitivity model. This review will discuss the role of 1,25(OH)2D3 as either a mediator of UVR‐induced immune suppression or as a photoprotective molecule against UVR‐induced DNA damage and immune suppression.

Activated signal transducer and activator of transcription-3 (STAT3) is a poor regulator of tumour necrosis factor-α production by human monocytes

Signal transducer and activator of transcription‐3 (STAT3) activation has been associated with suppressed inflammatory processes in experimental animals, murine myeloid cells and macrophage cell lines. Manipulation of STAT3 activity may therefore be a focus for pharmacological intervention of inflammatory diseases in humans. However, the ability of STAT3 to reduce the production of inflammatory mediators by activated human monocytes and macrophages has been characterized inadequately. To establish this, we used a recently optimized adenoviral approach to study the effect of overexpressed STAT3 or a transcriptionally inactive mutant STAT3 in lipopolysaccharide (LPS)‐stimulated human monocytes. STAT3 activated by LPS did not directly regulate inhibitor of kappa B α (IκBα) activation or tumour necrosis factor (TNF)‐α production, a process dependent on the transcriptional activity of nuclear factor kappa B (NFκB), although the transcriptional activity of STAT3 contributed to the mechanism by which interleukin (IL)‐10 suppressed LPS‐induced TNF‐α levels. This contrasted with the efficient block in IL‐10 induction of suppressor of cytokine signalling‐3 (SOCS3) in monocytes infected with an adenovirus expressing mutant STAT3. These results indicate that STAT3 activation cannot directly regulate LPS‐signalling in human monocytes and represents only part of the mechanism by which IL‐10 suppresses TNF‐α production by activated human monocytes. This study concludes that pharmacological manipulation of STAT3 transcriptional activity alone would be insufficient to control NFκB‐associated inflammation in humans.