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.

IL-17 is a proinflammatory cytokine that activates T cells and other immune cells to produce a variety of cytokines, chemokines, and cell adhesion molecules. This cytokine is augmented in the sera and/or tissues of patients with contact dermatitis, asthma, and rheumatoid arthritis. We previously demonstrated that IL-17 is involved in the development of autoimmune arthritis and contact, delayed, and airway hypersensitivity in mice. As the expression of IL-17 is also augmented in multiple sclerosis, we examined the involvement of this cytokine in these diseases using IL-17−/− murine disease models. We found that the development of experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis, was significantly suppressed in IL-17−/− mice; these animals exhibited delayed onset, reduced maximum severity scores, ameliorated histological changes, and early recovery. T cell sensitization against myelin oligodendrocyte glycoprotein was reduced in IL-17−/− mice upon sensitization. The major producer of IL-17 upon treatment with myelin digodendrocyte glycopritein was CD4+ T cells rather than CD8+ T cells, and adoptive transfer of IL-17−/− CD4+ T cells inefficiently induced EAE in recipient mice. Notably, IL-17-producing T cells were increased in IFN-γ−/− cells, while IFN-γ-producing cells were increased in IL-17−/− cells, suggesting that IL-17 and IFN-γ mutually regulate IFN-γ and IL-17 production. These observations indicate that IL-17 rather than IFN-γ plays a crucial role in the development of EAE.

IL-17 Plays an Important Role in the Development of Experimental Autoimmune Encephalomyelitis

Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease.

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.

Objective : To analyse proinflammatory Th1 and Th2 cytokines in patients with Behcet's disease (BD) in relation to disease activity. Methods : Forty-five BD patients (25 in active stage) were investigated with ELISA for estimation of cytokines levels. Furthermore, cytokines intracellular synthesis (IL-4 and IFN- &#110 ) of CD4 + T cells was studied. Results : Active and in remission BD patients showed increased serum levels of Th1 (IFN- &#110, IL-12) and Th2 (IL-4, IL-6 and IL-10) cytokines. Active BD was characterized by a higher increase of IL-6, IL-10 and a striking increase of IL-17, IL-18 and IFN- &#110, compared to remission BD. Upon in vitro stimulation, the percentages of CD4 + T cells containing IFN- &#110 and CD40L were higher in active BD compared to healthy controls. Conclusion : Our results suggest that the microenvironment of CD4 + T cells in active BD may induce the production of more cells committed to Th1 than in BD patients in remission and healthy controls.

Cytokine profile in Behçet's disease patients. Relationship with disease activity.

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

OBJECTIVES To analyze demographic, clinical and genetic features of Behcet's disease (BD) in Tunisia and to compare them with other ethnic and geographic groups. METHODS Two hundred and sixty patients with BD (International Study Group criteria) received in the Department of Internal Medicine of the University Hospital La Rabta in Tunisia, from 1987 to 2006, were retrospectively studied. Demographic, clinical, and genetic data were recorded and analyzed using SPSS 11.0. RESULTS The cohort consisted of 188 males and 72 females (M/F = 2.61). The mean age at the onset of the disease was 29 years. Oral and genital ulcers (GU) were seen in 100% and 83% respectively. The most other common clinical features of BD were ocular involvement (51%), arthritis (38.8%), venous thrombosis (33%) and neuropsychiatric symptoms (24.2%). Only 1.5% had gastrointestinal lesions. HLA-B51 frequency was significantly higher in patients with BD (54% vs. 25.5% in healthy controls, p < 0.05). DVT and pseudofolliculitis were significantly more frequent in men whereas arthritis and erythema nodosum were significantly more frequent in women. DVT was also significantly more frequent in patients with GU and those with neurological involvement. GU, positive pathergy test and DVT were significantly less frequent in patients with ocular involvement. Neurological involvement consisted of 47 cases with CNS parenchymal lesions and 22 with cerebral vascular lesions (13 had both lesions); HLA B51 was significantly less frequent in patients with neurological involvement. CONCLUSION Our series was characterized by particular aspects such as high frequency of DVT and neuropsychiatric involvement, and rare occurrence of gastrointestinal lesions. The results confirm the ethnic and geographic variation of BD expression.

Behçet's disease in Tunisia. Demographic, clinical and genetic aspects in 260 patients.

Background and objectives There is little knowledge about clinical and immunological variables associated with vitamin D insufficiency in inflammatory diseases. We sought to investigate disease variables associated with vitamin D levels in patients with Behcet's disease (BD) and its interaction with inflammatory responses. Methods One hundred and sixty BD patients (102 patients in active stage) were enrolled in a study assessing the relationship between serum vitamin D concentrations and disease activity. As control diseases we studied 22 Rheumatoid arthritis (RA) and 30 multiple sclerosis (MS) patients. Serum concentrations of vitamin D were assayed with a radioimmunoassay kit. To assess the correlation between inflammatory mediators, immune cell expression and vitamin D, 20 active BD patients and 18 healthy controls were investigated: T-cell subsets and Treg cells were quantified by flow cytometry. Th1/Th2 ratio and Th17 were studied by intracytoplasmic cytokines expression (IFN-γ, IL-4, IL-10 and IL-17). Results Decreased levels of vitamin D were observed in active BD patients compared to patients in the inactive stage and to healthy controls (p=0.0246; p=0.0001). A low significant difference was observed between inactive BD and healthy controls (p=0.004). Active BD expressed higher vitamin D levels than RA (p=0.007) and MS (p=0.044) patients (p=0.0238). In active BD, vitamin D levels were correlated with CRP and ESR. Serum levels of vitamin D correlated positively with the number of Treg cells (r=0.640; p=0.0024). The IFN-γ/IL-4 ratio (Th1/Th2) was inversely correlated with serum 25(OH)D levels (r=-0.599; p=0.0053). Conclusions Active BD was associated with lower serum Vitamin D levels. Our results showed that low levels of vitamin D were associated with a decrease in Treg cells and a skewing of the Th1/Th2 balance towards Th1. These findings suggest that vitamin D is an important promoter of T cell regulation in vivo in BD patients. As suggested in other inflammatory/autoimmune diseases, vitamin D may modulate inflammatory mediators.

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Vitamin D modulates peripheral immunity in patients with Behçet's disease.

Many studies have shown the implication of CD14 and toll-like receptors (TLRs) 2, 4 and 9 in the pathogenesis of asthma or atopy. To evaluate the association of CD14 and TLRs gene polymorphisms with asthma or atopy, 210 asthmatic children, 224 controls and 80 families were enrolled in this study. Six single nucleotide polymorphisms TLR2 (+2408 G-->A), TLR4 (+1196 C-->T), TLR4 (+896 A-->G), TLR9 (-1237 T-->C), TLR9 (-1486 T-->C) and CD14 (-159 C-->T) were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism in the case-control and family study. The -1237C allele in TLR9 gene polymorphisms was associated with increased risk of asthma [odds ratio 1.53, 95% confidence interval (1.03-2.27)], although no statistically significant differences in allele or genotype frequencies of four other TLRs polymorphisms were evident between the asthmatic and control groups. The CD14 -159 C allele was found to be significantly higher in the asthmatic group when compared with controls (P=0.0006<0.05). Transmission disequilibrium test of 80 asthmatic families showed significant transmission of the -159 C allele in the CD14 gene to asthma-affected offspring. It was concluded that TLR9 and CD14 gene polymorphisms may contribute to an inherited predisposition to asthma in Tunisian children.

Kamel Hamzaoui

Papers

Cytokine profile in Behçet's disease patients. Relationship with disease activity.

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

Behçet's disease in Tunisia. Demographic, clinical and genetic aspects in 260 patients.

Vitamin D modulates peripheral immunity in patients with Behçet's disease.

Toll-like receptors and CD14 genes polymorphisms and susceptibility to asthma in Tunisian children.