Interleukin-6: a possible inflammatory link between vitiligo and type 1 diabetes.

Vitiligo is a pigmentation disorder of unknown aetiology, but it has been reported in association with other autoimmune diseases including type 1 diabetes mellitus (T1D). Vitiligo and T1D share a common theory of autoimmunity, but still an inflammatory link between them remains to be investigated. This study investigates the status and contribution of the inflammatory markers tumour necrosis factor-α (TNFα), interleukin (IL)-6 and IL-1 in patients with vitiligo, T1D and vitiligo-associated T1D (Vt-T1D). The data showed that sera from Vt-T1D patients (n = 21) had higher levels of TNFα, IL-6 and IL-1ß compared with vitiligo patients (n = 39), T1D patients (n = 37) or controls (n = 42). Interestingly, serum levels of IL-6 were found to be significantly higher in Vt-T1D patients compared with the levels of TNFα and IL-1ß. These data also showed that IL-6 was high in Vt patients as compared to the levels of TNFa and L-1ß, whereas in T1D patients, IL-6 and TNFα were almost the same but were higher than IL-1ß. In conclusion, this is the first study to show an inflammatory link between vitiligo and T1D. The data conclude that IL-6 plays an important role in the pathogenesis of Vt-T1D patients and is likely to gain favour as a therapeutic target in these patients.

Physicochemical and immunological studies on mitochondrial DNA modified by peroxynitrite: implications of neo-epitopes of mitochondrial DNA in the etiopathogenesis of systemic lupus erythematosus.

BACKGROUND AND OBJECTIVE: Recent evidence has demonstrated that mitochondria possess their own nitric oxide synthase (mtNOS) and can produce endogenous reactive-nitrogen-species (RNS) including peroxynitrite (ONOO(-)). This study was undertaken to investigate the role of mitochondrial DNA (mtDNA) damage by ONOO(-) in systemic lupus erythematosus (SLE) autoimmunity. METHODS: MtDNA was isolated from fresh goat liver and modified by ONOO(-), generated by synergistic action of nitric oxide (NO) and superoxide (O (-) 2) donors. Modifications occurring in mtDNA were characterized by physicochemical techniques. SLE patients (n = 50) with varying disease activity according to the SLE Disease Activity Index (SLEDAI) and healthy controls (n = 34) were evaluated for antibodies to native and ONOO(-)-modified mtDNA by immunoassays. Gel retardation assays were performed to cross-examine the immunoassay results using affinity-purified SLE immunoglobulin G (IgG). Nitrosative stress in SLE patients was studied by measuring nitrotyrosine and inducible NO synthase (iNOS). RESULTS: The ONOO(-) caused extensive damage to mtDNA as evident by ultraviolet (UV) hyperchromicity and loss of florescence intensity. Thermal melting studies, agarose gel electrophoresis and nuclease S1 digestibility clearly indicate structural perturbation in mtDNA by ONOO(-). Quenching studies with specific NO or O (-) 2 quenchers confirmed that the damaging agent was ONOO(-). SLE autoantibodies exhibited enhanced binding with ONOO(-)-mtDNA as compared to their native analog. Interestingly, not only was there an increased number of subjects positive for ONOO(-) -mtDNA, but also the levels of anti-ONOO(-) -mtDNA antibodies were statistically significantly higher among SLE patients whose SLEDAI scores were ≥ 20 as compared with SLE patients with lower SLEDAI scores (SLEDAI < 20). Normal healthy controls showed negligible binding with either antigen. Furthermore, SLE patients had higher levels of nitrotyrosine and iNOS compared with their respective healthy controls. CONCLUSIONS: Our novel results provide an important insight into the immunological basis of anti-DNA autoantibody generation in SLE. Our data conclude that modification of mtDNA by ONOO(-) causes structural perturbations, resulting in the generation of neo-epitopes, and making it a potential immunogen in SLE. The mtDNA modified by ONOO(-) may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis.

Daily versus self-adjusted dosing of topical mometasone furoate nasal spray in patients with allergic rhinitis: randomised, controlled trial.

BACKGROUND: Many patients with allergic rhinitis are reluctant to use daily intranasal steroids for prolonged periods. A self-adjusted regimen which delivers reasonable control of allergic rhinitis may be more acceptable to such patients. OBJECTIVES: To compare the efficacy of daily use of mometasone furoate nasal spray, versus a self-adjusted regimen, in patients with chronic allergic rhinitis, in terms of symptom control and nasal volume change. SETTING: Ambulatory visits in an office setting. PATIENTS AND METHODS: Sixty patients with chronic allergic rhinitis were randomised: 30 were prescribed mometasone furoate nasal spray once daily for six weeks, while 30 were prescribed the same spray daily for one week, every alternate day for one week and then on a self-adjusted regimen for four weeks. Patients kept a symptom diary documenting sneezing, rhinorrhoea, nasal blockage and nasal itching. Acoustic rhinometry was used to measure the total nasal cavity volume at the first visit and at the end of the treatment period. RESULTS: The total nasal score on treatment days showed an improvement in both groups, compared with baseline measurements. There was no significant difference in total nasal scores between the two groups, except on days 10 (p = 0.043), 20 (p = 0.008), 23 (p = 0.19), 30 (p = 0.008) and 37 (p = 0.000), when the daily group's total nasal score was significantly lower than the self-adjusted group's total nasal score, and on day 8 (p = 0.004), when the self-adjusted group's total nasal score was significantly lower than the daily group's total nasal score. Total nasal cavity volume significantly increased in both groups (p = 0.0001), with no statistically significant difference between the groups. CONCLUSIONS: Self-adjusted dosage of mometasone furoate nasal spray gives reasonable control of allergic rhinitis (albeit with some 'breakthrough' symptoms). Patients should learn how to control these symptoms with the least number of steroid doses.