Altered peripheral toll-like receptor responses in the irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a stress-related disorder with disturbed brain-gut communication, gastrointestinal homeostasis and, based on recent evidence, low grade inflammation and an altered microbiota. The immune system is a critical regulator of the brain-gut axis. Toll-like receptors (TLRs) are pattern recognition molecules regulating innate immunity. AIM: To characterise toll-like receptor activity in IBS. METHODS: Thirty IBS patients and 30 healthy controls (HC) were recruited. Venous blood was collected, and cultured with a panel of toll-like receptor agonists for 24 h. Cell supernatants were analysed using a multiplex ELISA approach to measure IL1ß, IL6, IL8 and TNFα. Plasma was analysed for levels of inflammatory cytokines and cortisol. RESULTS: Toll-like receptor agonist-induced cytokine (IL1ß, IL6, IL8 and TNFα) release was markedly enhanced in stimulated whole blood from IBS (n = 30) patients compared with healthy controls (n = 30). An exaggerated response to the TLR8 agonist for all cytokines investigated was seen in IBS patients. In addition, enhanced TLR2-induced TNFα release, TLR3-induced IL-8 release, TLR4-induced IL1ß and TNFα release, TLR5-induced IL1ß and TNFα release and TLR7-induced IL-8 release were also observed in IBS patients. No differences in TLR1, TLR6 or TLR9 activity were detected. In addition, plasma levels of cortisol, IL-6 and IL-8 were significantly increased in IBS patients. CONCLUSION: Taken together, these data demonstrate elevated cytokine levels and toll-like receptor activity in the periphery of patients with the irritable bowel syndrome, indicating some immune dysregulation in these patients.

Enhanced peripheral toll-like receptor responses in psychosis: further evidence of a pro-inflammatory phenotype.

Low-grade peripheral inflammation is often present in psychotic patients. Toll-like receptors (TLRs) are pattern-recognition molecules that initiate inflammation. Our objective was to investigate the peripheral TLR activity in psychosis. Forty schizophrenia patients, twenty bipolar patients and forty healthy controls (HC) were recruited. Donated whole blood was cultured with TLR agonists for 24 h. Cell supernatants were analysed using a multiplex enzyme-linked immunosorbent assay approach to measure IL-1ß, IL-6, IL-8 and tumour necrosis factor-α (TNFα). Plasma was analysed for cytokines, cortisol and acute phase proteins. Here, we show that selective TLR agonist-induced cytokine (IL-1ß, IL-6, IL-8 and TNFα) release is enhanced in stimulated whole blood from schizophrenia and bipolar patients compared with HC. An exaggerated release of IL-1ß, IL-6 and TNFα following treatment with the TLR2 agonist HKLM was detected in both disorders compared with controls. Enhanced TLR4-induced increases in IL-1ß for both disorders coupled with TNFα increases for bipolar patients were observed. TLR8-induced increases in IL-1ß for both disorders as well as IL-6 and TNFα increases for bipolar patients were detected. TLR9-induced increases in IL-8 for schizophrenia patients were also observed. No differences in TLR1, TLR3, TLR5, TLR6 or TLR7 activity were detected. Plasma levels of IL-6 were significantly elevated in bipolar patients while TNFα levels were significantly elevated in schizophrenia patients compared with controls. Plasma acute phase proteins were significantly elevated in bipolar patients. These data demonstrate that specific alterations in TLR agonist-mediated cytokine release contribute to the evidence of immune dysfunction in psychotic disorders.

[Reliability of clinical diagnosis in malignant melanoma]. / A klinikai diagnózis megbízhatósága melanoma malignumban.

During the last 10 years (1981-1990) 14,178 skin tumors were histologically examined in the Department of Dermatology of the University Medical School of Szeged. Of these lesions 520 were diagnosed clinically and histologically as malignant melanoma (true-positive). 104 lesions were clinically diagnosed as malignant melanoma but were found histologically to be other tumors (false-positive). An additional 78 cases diagnosed clinically as other than malignant melanomas, were found histologically to be malignant melanoma (false-negative). The clinical diagnostic accuracy was 74.07%. The index of suspicion was 104.34%, thus demonstrating a slight degree of "overdiagnosis". The sensitivity, specificity and predictive values were consonant with those of the literature.