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• Novel potential role of neuropeptides in the pathogenesis of psoriasis and as new therapeutic targets

Background: Effective and safe products are needed for long-term management of scalp psoriasis. This study investigated the long-term safety and efficacy of a two-compound formulation (calcipotriol 50 µg/g plus betamethasone dipropionate 0.5 mg/g) for scalp psoriasis. Methods: In this 52-week, international, double-blind study, 869 patients with moderate-to-severe scalp psoriasis were randomized to either a two-compound scalp formulation (n = 429) or calcipotriol (n = 440). Results: Adverse drug reactions were less frequent in the two-compound group compared with the calcipotriol group (17.2 vs. 29.5%; p < 0.001). Incidences of adverse events possibly associated with long-term corticosteroid use were low in both the two-compound (2.6%) and the calcipotriol (3.0%) groups. Disease was satisfactorily controlled in 92.3% of visits in the two-compound group versus 80.0% in the calcipotriol group (p < 0.001). Conclusion: The two-compound scalp formulation demonstrated a high level of safety and efficacy in long-term management of scalp psoriasis.

The study objectives were to investigate serum levels of interleukin-6 and C-reactive protein (CRP) after liver transplantation to correlated measurements with various clinical parameters. Twenty-three patients were studied after orthotopic liver transplantation. Serum IL-6 activity was evaluated by testing its capacity to induce proliferation of the IL-6-dependent hybridoma cell line B9. CRP was assessed by a nephelometric method. Only two of seven patients with acute cellular rejection developed an increase of serum IL-6 and CRP. In contrast to this rejection group, elevated IL-6 levels were observed in 7/9 patients with bacterial infections. Peak values for IL-6 were observed one day and for CRP two days after clinical diagnosis of infection. CMV disease was also associated with markedly increased IL-6 and CRP levels in 5/7 patients. Surprisingly, levels in this condition were approximately in the same range as in bacterial infection. IL-6 and CRP serum levels seen in bacterial infection and CMV disease were significantly higher than those in rejection (P less than 0.001). Serum IL-6 activity was neutralized by an antiserum directed against recombinant human IL-6. Preferential elevations of IL-6 and CRP represent one feature of bacterial and viral infections. Elevation of TNF during rejection as described earlier is only rarely accompanied by increased serum IL-6 levels.

The utility of high-performance liquid chromatography (HPLC) in the purification of Interleukin 1 (IL 1, lymphocyte-activating factor) has been investigated Human IL 1-containing supernatants were concentrated by lyophilization and desalted using Bio-Gel P-6 DG desalting gel. Subsequently, the sample containing IL 1 activity was subjected to HPLC with a novel HPHT hydroxylapatite column. Using a sodium phosphate gradient, IL 1 was eluted as a single peak of activity separated from the major protein contaminant, yielding 90% recovery and a specific activity of 6.3 X 10(4) U/mg. Pooled fractions from Bio-Gel HPHT were concentrated and subjected either to Bio-Sil IEX 540 DEAE anion-exchange or Bio-Sil TSK 125 size exclusion chromatography. From DEAE the IL 1 activity was eluted before a linear sodium chloride gradient was started, whereas the protein contaminant was eluted at 110 mM NaCl. When TSK was used IL 1 activity was eluted within a molecular weight range of 20,000-10,000. Fractions from the DEAE or TSK columns that were positive for IL 1 activity did not contain detectable protein, suggesting a good resolution. Furthermore, the recovery from DEAE was 26% whereas TSK 125 yielded 119% of the original activity. The specific activities were 6 X 10(7) and 2.5 X 10(8) U/mg, respectively. Thus, this method provides a rapid and reproducible procedure for the purification if IL 1 for further biological characterization.

In a pilot study, serum ferritin levels of patients with malignant melanoma were found to be increased in stage III of the disease. Therefore, serial determinations were carried out up to 24 months in patients at various stages of the disease undergoing either chemo- or immunotherapy. Serum ferritin was determined by a two-site IRMA technique. Serum samples of 91 patients in different clinical stages of histologically verified malignant melanoma were included in these investigations. 80 healthy individuals were also investigated to determine normal ranges of serum ferritin. In stage III serum ferritin levels were significantly elevated (p less than 0,0005), whereas in stages I and II the values were within the normal range. Repeated serum ferritin levels of 10 patients in stage I and 13 patients in stages II and III without evidence of tumor progression were within the normal range. In 9 patients in stage III the increases in serum ferritin concentration correlated with the degree of dissemination of metastasis. Because of the occurrence of increased ferritin levels only in melanoma patients with progressive metastatic disease, the measurement of serum ferritin might have limited utility in clinical evaluation of melanoma patients as well as in the prediction of recurrence and in monitoring response to therapy.