Altered expression of IL-10 family cytokines in monocytes from CRMO patients result in enhanced IL-1ß expression and release.

Chronic recurrent multifocal osteomyelitis (CRMO) is characterized by reduced activation of protein kinases ERK1 and 2 in monocytes resulting in impaired IL-10 expression. IL10 and its homologs IL19 and IL20 are organized in the IL10 cluster on chromosome 1q32. IL-10 and IL-19 are immune-regulatory cytokines, while IL-20 acts in a pro-inflammatory manner. The NLRP3 inflammasome, a multi-protein complex forming in response to innate stimuli, mediates IL-1ß cleavage and release. Here, we investigated IL-10-related cytokine expression in CRMO monocytes, underlying molecular events, and effects on inflammatory responses. We observed reduced anti-inflammatory IL-10 and IL-19 expression, and enhanced IL-20 expression in CRMO monocytes. Reduced IL-10 and IL-19 expression was associated with impaired Sp-1 recruitment to regulatory regions, contributing to NLRP3 inflammasome activation, which may induce inflammatory bone-loss. Our findings underscore the importance of balanced receptor-, cell-, and tissue-specific cytokine expression for immune homeostasis, providing additional arguments for cytokine blocking strategies in CRMO.

The efficacy of amineptine in the treatment of depressive patients with irritable bowel syndrome.

Patients with irritable bowel syndrome (IBS) often suffer from depression. In view of this, the effect of amineptine on the psychopathological condition of depressive patients with IBS was studied. Forty patients who satisfied the criteria for irritable bowel syndrome and had a Hamilton 24-item score above 15 were randomly assigned to receive either amineptine 200 mg/day or placebo in a double-blind clinical trial. Patients on amineptine were more improved at the end of the trial than patients on placebo (total Hamilton score). Amineptine was more effective on depressive mood, retardation, and cognitive dysfunction. Although these findings should be interpreted with caution because the baseline scores were higher in the amineptine than in the placebo group, they provide some evidence that amineptine may be a useful tool for the management of depressive patients with IBS.

The detection of glucocorticoid receptors in breast cancer by immunocytochemical and biochemical methods.

Glucocorticoid receptors have been detected in 90 human breast tumors and tumor-like conditions by the immunoperoxidase method using a specific antibody against the glucocorticoid receptor isolated from rat thymocytes. In some of the specimens the [3H]-dexamethasone binding assay was also performed and the results obtained were compared with those of the immunoperoxidase method. When the biochemical method was used, no strict correlation between the degree of binding of [3H]-dexamethasone and malignancy on the basis of histological findings could be demonstrated. In contrast, the immunoperoxidase method was in full agreement with the histological type of the tumor. Thus, nearly all malignant breast tumors (carcinomas) were positive by the immunoperoxidase method to a vary degree. Most of the examined benign tumor-like conditions (fibrocystic disease) were found to be negative. Intermediate situations, such as atypical duct of lobular hyperplasia, papillomatosis etc, were mostly positive. These findings suggest that ther immunoperoxidase method, part from its usefulness for the detection of glucocorticoid receptors in breast tissue, may be used as an early biological marker to detect early conversion of normal to hyperplastic tissue and/or malignancy of the mammary gland.

Activation of the alternative pathway of human complement by the extracellular slime glycolipoprotein of Pseudomonas aeruginosa.

The capability of the extracellular slime glycolipoprotein (GLP) of Pseudomonas aeruginosa to activate human complement was investigated. When slime GLP was added to type AB human serum, C3 and factor B were converted to their respective major cleavage fragments, C3b and Bb. This activation also occurred when slime GLP was incubated with serum-ethylene glycol bis(trichloroacetate)-Mg++, a result which indicates that the alternative complement pathway is involved. Additional support for the hypothesis of alternative pathway activation was provided by the fact that when serum-ethylene glycol bis(trichloroacetate)-Mg++ was preheated to inactivate factor B, slime GLP did not induce conversion of C3. The activation of the alternative pathway of human complement by slime GLP may represent an early nonimmune defense against P. aeruginosa infection.