Objective. To investigate the presence and role of interleukin-17 (IL-17) in rheumatoid arthritis (RA), and its regulation by antiinflammatory cytokines.Methods. The production of IL-17 was measured in supernatants of RA, osteoarthritis (OA), and normal synovial tissue pieces cultured ex vivo. Quantification of IL-17 was performed using a specific biologic assay. IL-17 gene expression was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR)-techniques. Immunohistochemistry was used to evaluate the frequency of IL-17-positive cells in synovium.The secretion of IL-17 by synovium was measured in the presence of IL-4, IL-13, and IL-10. In addition, the contributions of exogenous and endogenous IL-17 to IL-6 production by RA synovium were studied.Results. Functional IL-17 was spontaneously produced by 16 of 18 RA (mean ؎ SEM 41.7 ؎ 11.4 units/ml), 2 of 12 OA (5.3 ؎ 4.5 units/ml), and 0 of 3 normal synovial explant cultures. IL-17 messenger RNA expression was demonstrated by RT-PCR in 4 of 5 RA and 0 of 3 OA synovial samples. By immunostaining of RA synovium, IL-17-producing cells were found in the T cell-rich area. Addition of both IL-4 and IL-13 completely inhibited the production of IL-17, whereas IL-10 had no effect. Addition of exogenous IL-17 to RA synovium resulted in an increase in IL-6 production, whereas that of a blocking anti-IL-17 antibody reduced production of IL-6.Conclusion. The T cell cytokine IL-17 was found to be highly produced by RA, but not by OA, synovium. Its production and function were down-regulated by IL-4 and IL-13. These results indicate that IL-17 contributes to the active, proinflammatory pattern that is characteristic of RA. Through the contribution of IL-17, some Th1-like T cells appear to mediate synovial inflammation.

Prostate cancer is the most common malignancy in elderly men and is often complicated by osteosclerotic metastases. Bone scintigraphy is commonly used to assess the extent of bone metastases; its use is limited in monitoring of treatment efficacy because it is an expensive, time-consuming technique that does not reflect the rapid skeletal response to therapy (Coleman, 1998). The bone scan flare response following successful therapy also reduces the value of bone scanning in the early monitoring of treatment in prostate cancer (Pollen et al, 1984). The serum level of prostatespecific antigen is the most sensitive index of disease progression in most but not all patients, but does not reflect the effects of palliative treatments such as bisphosphonates for bone metastases in patients that escape from antihormonal therapy.The marked increase of osteoblastic activity in patients with osteosclerotic metastases is reflected by increased levels of serum total and bone-specific alkaline phosphatase (Pecherstorfer et al, 1995;Lorente et al, 1996). There is, however, biochemical (Myamoto et al, 1994, Sano et al, 1994Kylmala et al, 1995;Berruti et al, 1996;Ikeda et al, 1996;Takeuchi et al, 1996;Maeda et al, 1997;Nguyen-Pamart et al, 1997, Pelger et al, 1998 and histological (Urwin et al, 1985;Clarke et al, 1991) evidence of increased bone resorption in these patients even in the absence of overt osteolytic bone metastases. This increased bone resorption is of clinical relevance as it is the rationale for using bisphosphonates, a palliative treatment that has been shown to reduce bone pain in patients with progressive metastatic prostate cancer who no longer respond to hormonal therapy (Adami et al, 1985;Carey and Lippert, 1988;Clarke et al, 1992;Kylmala et al, 1993, Taube et al, 1994Pelger et al, 1998).In this study we assessed the level of bone resorption in patients with osteosclerotic metastases from prostate cancer before and after bisphosphonate treatment by using new sensitive and specific biochemical markers of bone resorption including a serum assay for type I collagen C-telopeptide breakdown products; and values were compared to those of bone formation markers. PATIENTS AND METHODSForty-eight patients with carcinoma of the prostate (age 71.7 ± 9.6 years, mean ± 1 s.d.) and nine with benign prostatic hyperplasia (BHP) (age 69.8 ± 4.2 years) were enrolled. All patients with cancer had a prostatic biopsy and tissue diagnosis of adenocarcinoma. Bone involvement and its extent was evaluated by bone scintigraphy using Technetium-99m labelled methylene bisphosphonate. When bone metastases were suspected, confirmation was obtained with standard radiographs, computerized tomography (CT) and/or magnetic resonance imaging. The metastatic load in Summary Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to tha...

The balance between interleukin-1 (IL-1) and its competitive antagonist IL-1 receptor antagonist (IL-1Ra) may contribute to the pathogenesis of rheumatoid arthritis (RA). We analysed the frequency of different alleles in the IL-1B gene (at -511 and at +3954) as well as in the IL-1Ra gene (at +2018) in an association study involving 297 RA patients and 112 healthy controls from the same geographic area. We tested associations with RA susceptibility or severity, and with circulating levels of IL-1Ra and IL-1beta. Carriage of the rare IL-1B (+3954) allele 2 was increased in destructive arthritis (DRA) as compared to non-destructive arthritis (NDRA) (OR 1.7, 95% CI 1.1-2.8, 49.0% vs 35.9%) and controls (OR 1.7, 95% CI 1.1-2.8, 35.8%). Patients carrying this allele had a more destructive (Larsen wrist radiological index: mean +/- s.e.m., 2.1 +/- 0.2 vs 1.6 +/- 0.1, P = 0.005; Steinbrocker functional index: 2.4 +/- 0.1 vs 1.9 +/- 0.1, P = 0.002) and active disease (Ritchie articular index: 8.1 +/- 0.8 vs 5.3 +/- 0.6, P = 0.002; erythrocyte sedimentation rate (ESR): 36.6 +/- 2.9 mm/h vs 25.3 +/- 1.8 mm/h, P = 0.002). This contribution was independent from that of HLA DR4/DR1 to severity. IL-1Ra plasma levels adjusted to ESR values were significantly lower in IL-1B2 (+3954) positive than negative RA patients (1.0 +/- 0.1 vs 1.2 +/- 0.1 ng/ml, P = 0.01). This IL-1B (+3954) gene polymorphism may be an important marker for the severity of joint destruction in RA and is associated with an imbalance in IL-1Ra production. As this genetic association was independent and additive to the risk of HLA DR4/DR1 status, it could be a useful addition to HLA-DR4/1 as a genetic prognostic marker early in the course of the disease.

In a meta-analysis of observational studies of patients with acute diverticulitis, we found the pooled prevalence of colorectal cancer to be 1.9%. The risk of colorectal cancer was significantly higher in patients with complicated diverticulitis than in patients with uncomplicated diverticulitis.

ObjectiveThe objective of this study was to review the records of patients with excised abdominal wall endometriosis (AWE) to determine patient characteristics, diagnostic methods, presence of concurrent pelvic endometriosis and type of surgery.Study designMedical records from an 11-year period were searched to identify histologically confirmed AWE cases. Descriptive data were collected and analyzed. Two subgroups were differentiated: isolated AWE and pelvic endometriosis-associated AWE.ResultsThirty-five women with AWE were included. The most common symptom was cyclic abdominal or parietal pain (68.6%); 17.1% of the women had no symptoms. Twenty-nine women (82.8%) had a history of gynecological or obstetrical surgery, most commonly cesarean section (CS). The mean interval between prior surgery and appearance of symptoms was 5.3 years. Six women (17.1%) had no prior surgery; all six presented with umbilical nodules, nulliparity and confirmed mild to severe pelvic endometriosis. Among all patients, 34.3% had concurrent pelvic endometriosis, 40% presented with isolated AWE and 25.7% had no pelvic exploration. Women with concurrent pelvic endometriosis had significantly lower parity, smaller nodule size and a higher likelihood of umbilical location than those with isolated AWE (p < 0.05). A history of CS was more commonly found in women with isolated AWE. The overall recurrence rate over the study period was 11.4%, with a mean follow-up period of 5.2 years.ConclusionsAWE is an uncommon condition associated with long diagnostic and therapeutic delays. In patients with umbilical AWE and no surgical history, pelvic endometriosis is commonly present and should be highly suspected.