admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

Van Eerdewegh P, Little RD, Dupuis J, et al Nature 2002;418:426–430 

To identify novel genetic polymorphisms associated with bronchial hyperresponsiveness (BHR) in asthma

Four hundred sixty white affected sib-pair families from the United States and the United Kingdom with current asthma

A genetic linkage analysis was performed for current asthma and BHR Case-control, transmission disequilibrium, and haplotype analyses were conducted to identify the gene(s) most commonly associated with asthma Novel genes of interest were …

Association of the adam33 gene with asthma and bronchial hyperresponsiveness

The interleukin-1 (IL-1) family of cytokines and receptors is unique in immunology because the IL-1 family and Toll-like receptor (TLR) families share similar functions. More than any other cytokine family, the IL-1 family is primarily associated with innate immunity. More than 95% of living organisms use innate immune mechanisms for survival whereas less than 5% depend on T- and B-cell functions. Innate immunity is manifested by inflammation, which can function as a mechanism of host defense but when uncontrolled is detrimental to survival. Each member of the IL-1 receptor and TLR family contains the cytoplasmic Toll-IL-1-Receptor (TIR) domain. The 50 amino acid TIR domains are highly homologous with the Toll protein in Drosophila. The TIR domain is nearly the same and present in each TLR and each IL-1 receptor family. Whereas IL-1 family cytokine members trigger innate inflammation via IL-1 family of receptors, TLRs trigger inflammation via bacteria, microbial products, viruses, nucleic acids, and damage-associated molecular patterns (DAMPs). In fact, IL-1 family member IL-1a and IL-33 also function as DAMPs. Although the inflammatory properties of the IL-1 family dominate in innate immunity, IL-1 family member can play a role in acquired immunity. This overview is a condensed update of the IL-1 family of cytokines and receptors.

Overview of the IL-1 family in innate inflammation and acquired immunity.

Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels. This includes (i) the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with transcription factors, such as NF-κB, which regulate the expression of inflammatory genes and (iii) the activation of signaling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signaling and other signaling cascades involved in inflammation. An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP), ChIP-seq, and FAIRE-seq.

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Vitamin D in inflammatory diseases

More than any other cytokine family, the 11 members of the IL-1 family are associated with innate immune responses, which occur in acute inflammation and chronic inflammatory conditions such as rheumatic diseases. In many rheumatic diseases, the severity of the condition can result from the balance between the pro-inflammatory and anti-inflammatory members of the IL-1 family. Pro-inflammatory family members (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β and IL-36γ) are found in the articular environment during arthritis and often correlate with the degree of inflammation present. IL-1β has emerged as pivotal for promoting inflammation, particularly in autoinflammatory diseases, whereas IL-1α and the IL-36 subfamily are associated with skin diseases. IL-33 regulates T helper 2 (TH2) cell-mediated diseases, in sharp contrast to IL-18, which mainly regulates TH1 cell-mediated responses. The IL-1 family also contains four members that suppress inflammation: two specific receptor antagonists (IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra)), and two members that broadly suppress innate inflammation by non-specifically reducing several cytokines and chemokines (IL-37 and IL-38). In this Review, each of the eleven IL-1 family cytokines and their receptors are discussed, along with their putative roles in rheumatic disease and therapeutic options for targeting or promoting these cytokines. Cytokines from the IL-1 family perform important functions in innate immune reactions, but can also be involved in chronic inflammatory diseases. This Review highlights the roles of IL-1 family members in rheumatic diseases and potential therapeutic approaches to targeting them.

The IL-1 family of cytokines and receptors in rheumatic diseases.

Anti-inflammatory activity of IL-37 in asthmatic children: Correlation with inflammatory cytokines TNF-α, IL-β, IL-6 and IL-17A.

Background
Vitamin D exerts profound effects on both adaptive and innate immune functions involved in the development and course of autoimmune and inflammatory diseases. As the incidence of vitamin D insufficiency is surprisingly high in the general population, experimental studies have started to investigate whether vitamin D levels (measured as serum 25 hydroxy vitamin D-25[OH]D) are correlated with immune cells and clinical parameters.

/pdf/the-impact-of-vitamin-d-deficiency-on-immune-t-cells-in-1sf6bnykmk.pdf

The impact of vitamin D deficiency on immune T cells in asthmatic children: a case-control study

Association of vitamin D receptor gene polymorphisms with susceptibility to asthma in Tunisian children: A case control study

BACKGROUND Asthma is a chronic inflammatory disorder, hypothetically caused by autoreactive Th2 cells, whereas Th1 and regulatory T cells may confer protection. The development of Th subpopulations is dependent on the expression of lineage-specific transcription factors. PURPOSE This study aimed to assess the balance of CD4(+) T cell populations in asthmatic children. METHODS Peripheral blood mononuclear cells (PBMC) mRNA expression was assessed in 30 asthmatic children (18 patients with mild asthma and 12 with moderate asthma). Real-time polymerase chain reaction (RT-PCR) quantified TBX21, GATA-3, RORC, FOXP3, and EBI3 mRNA expression. Intracellular cytokine expression of IL-2, IL-4, IL-10, and IFN-γ in CD4(+) T cells in asthmatic children was measured by flow cytometry. IL-6 and IL-17 cytokines were assessed in serum by enzyme-linked immunosorbent assay (ELISA). RESULTS A significant increase was found in the percentage of CD4(+) and CD8(+) T cell-producing IL-4, IL-6, and IL-17. A decreased percentage of CD4(+) producing IFN-γ in asthmatic children was found. Expression of GATA-3 (Th2), retinoid-related orphan receptor C (RORC) (Th17), and EBI3 were increased in asthmatic patients compared to healthy controls. Expression of FOXP3 (Treg) and TBX21 (Th1) were decreased (P < 0.0001 and P < 0.0001) in asthmatic children. Analysis of transcription factor ratios revealed an increase in the RORC/FOXP3 (P = 0.0001), and a significant decrease of TBX21/GATA-3 (P = 0.0001) ratios in patients with asthma. CONCLUSION Young asthmatics were characterized by increased IL-4 production and low IFN-γ synthesis. The increased serum IL-17 and IL-6 levels sustained an inflammatory environment in young asthmatics. The results indicate that FOXP3 and RORC mRNA expression could be associated with the sustained inflammatory process, transduced by low immune tolerance by Treg cells. The TBX21/GATA-3 and RORC/FOXP3 ratios dysregulation in asthmatics is consistent with the plasticity existing between Th1, Th17, and Treg cells during inflammation.

https://www.dovepress.com/getfile.php?fileID=11369

Transcriptional characteristics of CD4+ T cells in young asthmatic children: RORC and FOXP3 axis

As childhood tuberculosis (TB) reflects recent transmission, its burden provides an accurate measure of the level of TB control achieved in a particular community. Moreover, infected children represent the main reservoir of Mycobacterium tuberculosis (MTB) as potential future cases. However, childhood TB is neglected by scientists, policy makers, healthcare professionals and product developers [1]. Moreover, the interests of individual patients and public health may be conflicting. As children are considered in the majority of cases as noncontagious, asymptomatic disease is frequently ignored [2]. This is why, in 2013, the World Health Organization (WHO) developed a roadmap aiming to achieve zero deaths due to childhood TB by 2025 [3]. This article aims to highlight the underestimated reality of childhood TB, emphasising improved diagnosis possibilities and new treatment modalities, and advocating for dedicated paediatric operational research and clinical trials.

Active scanning of the recent literature using the keywords: “children tuberculosis”, “latent tuberculosis infection”, “new diagnosis tools” and “treatment modalities” was performed using PubMed and EMBASE. In addition, International Union Against Tuberculosis and Lung Disease publications were screened and WHO policy and guidance documents on TB were obtained from the WHO website (http://www.who.int).

Each year, more than 74 000 children die from TB [3]. Exposure to an adult with pulmonary TB was reported to increase mortality by 70% in children under 5 years of age in high-burden settings and by eight-fold when the mother had TB [4].

The global burden of childhood TB is under-reported due to paucibacillary disease and the difficulty of confirming the diagnosis. In China, the prevalence rates for bacteriologically positive pulmonary TB and smear-positive cases were eight and 13 times less than the clinically diagnosed pulmonary TB rate, respectively [5]. TB disease and latent TB infection …

https://err.ersjournals.com/content/errev/23/133/278.full.pdf

Anissa Berraies

Papers

Anti-inflammatory activity of IL-37 in asthmatic children: Correlation with inflammatory cytokines TNF-α, IL-β, IL-6 and IL-17A.

The impact of vitamin D deficiency on immune T cells in asthmatic children: a case-control study

Association of vitamin D receptor gene polymorphisms with susceptibility to asthma in Tunisian children: A case control study

Transcriptional characteristics of CD4+ T cells in young asthmatic children: RORC and FOXP3 axis

Childhood tuberculosis: a concern of the modern world