51Cr-EDTA activity was measured in urine and blood of patients receiving non-steroidal anti-inflammatory (NSA) drug treatment and of healthy subjects and other patients (controls), after oral intake of 51Cr-EDTA, for the purpose of deciding whether NSA treatment increases urinary excretion of oral 51Cr-EDTA as an expression of increased intestinal permeability. 51Cr-EDTA activity in urine and blood of patients with rheumatoid arthritis (13) being treated with NSA was significantly higher (similar to results in 13 patients with Crohn's disease) than that of a control group (14) of patients with rheumatoid arthritis without such treatment (9) and patients without rheumatic disease (5). Both in patients with rheumatoid arthritis receiving NSA drugs and patients with Crohn's disease there was a highly significant correlation between urinary and blood activity. There was no effect of NSA drugs on renal function. The results indicate that NSA drugs increase interenterocytic permeability to an extent comparable to permeability abnormalities in Crohn's disease.

Background: There is no established therapy for maintaining remission in patients with Crohn's disease. Following different suggestions from the literature, two potential interventions for maintaining remission were tested against placebo, using either 5 g/day of a highly concentrated omega-3 fatty acid compound or a carbohydrate-reduced diet (84 g/day). Methods: A total of 204 patients were recruited after they had had an acute relapse. After remission (CDAI less than or equal to 150) was attained with steroid therapy, patients were randomized to receive either omega-3 fatty acids (n = 70), placebo (n = 65), or diet (n = 69). Low-dose prednisolone was given to all patients for the first 8 weeks of intervention, CDAI and an acute-phase protein (CRP) were used as criteria for a relapse. Results: The proportion of patients without relapse within a year were similar in the placebo and active treatment group (intention-to-treat analysis: placebo, 30%; active treatment, 30%; protocol-adhering patients, 29% versus 28%). Patients did gain benefit (53%; p = 0.023) for as long as they maintained the diet. However, intention-to-treat analysis (diet group, 40%) did not show a noticeable difference when compared with placebo. Conclusions: Omega-3 fatty acids did not show an effect on extending the remission in Crohn's disease. For the diet patients the question remains whether the noncompliant patients dropped out early because they sensed a relapse approaching or whether their condition deteriorated because they failed to comply with the diet.

Acute exacerbations of chronic inflammatory bowel disease (ulcerative colitis and Crohn's disease) are characterised by an increase in immunoglobulin G (IgG) positive cells in the mucosa, whereas uninflamed mucosa of inflammatory bowel disease patients displays only moderately increased or normal numbers of these cells. Previous data suggest that acute exacerbations of ulcerative colitis and Crohn's disease can be distinguished by different IgG subclass expression of mucosal immunocytes and a different IgG subclass production pattern of lamina propria lymphocytes. A procedure to obtain enough intestinal mononuclear cells from biopsy specimens to measure in vitro IgG and IgG1 production in control subjects and various patient groups has been established. IgG2 could be measured in Crohn's disease and ulcerative colitis only, as the concentrations in control subjects were below the sensitivity of the ELISA method. We found that IgG and IgG1 production correlated with the degree of local inflammation in both diseases, even in slightly inflamed mucosa, compared with control subjects. The proportion of IgG1 subclass was significantly increased in severely inflamed mucosa of both ulcerative colitis and Crohn's disease patients. A major difference between Crohn's disease and ulcerative colitis mucosa is apparent in mild or no inflammation. In Crohn's disease mucosa in remission, the IgG1/IgG ratio is comparable with that in controls, yet ulcerative colitis mucosa still displays significantly increased proportions of IgG1. In addition, the IgG2/IgG ratio is 0.12 in ulcerative colitis and 0.19 in Crohn's disease patients. The results show the dependence of local IgG and IgG1 production on the degree of inflammation and that an increase in subclass IgG1 in ulcerative colitis is present at all stages, including remission. These findings support the hypothesis that different immunoregulatory mechanisms are involved in Crohn's disease and ulcerative colitis. Environmental stimuli or genetic background may be responsible for the observed differences.

The influence of cefodizime (CDZ) on spontaneous cell-mediated cytotoxicity (SCMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) was investigated in nine patients with conditions predisposing to infection (T-cell deficiency, humoral immune deficiency, myeloproliferative syndrome, kidney or liver damage, or chronic pulmonary disease). SCMC, using the K562 and LIK cell lines as targets, and ADCC, using the LIK cell line, were measured at baseline and after ten days of therapy with CDZ for lower respiratory tract infections. Six patients were cured; clinical outcome was not evaluable in the other three. SCMC lysis of K562 cells did not change significantly. SCMC and ADCC lysis of LIK (lymphoblastoid) cells both increased significantly. CDZ selectively stimulated a subpopulation of NK cells in this population of immunocompromised patients with lower respiratory tract infections.

The effector function of immunocompetent cells in the gut mucosa has not yet been defined. The cytotoxic function of these cells might be important in the normal immune response and could be relevant to the mucosal damage seen in inflammatory conditions. The cytotoxic function of isolated intraepithelial and lamina propria mononuclear cells in six and 18 hour assays after the addition of various stimuli that interact with the human leukocyte antigens CD2 and CD3 on the mucosal effector cells was investigated. T cell phenotypes were determined using CD4, CD8, and HML1 to characterise cells of the appropriate compartments. Anti-CD3 and phytohaemagglutinin can induce toxic activity of lamina propria lymphocytes in most individuals after six hours and in all individuals after 18 hours. Anti-CD2, anti-CD3, and phytohaemagglutinin are similarly effective at triggering lamina propria lymphocytes. Intraepithelial lymphocytes contain predominantly CD8 and HML1 positive T cells, differentiating phenotypically intraepithelial lymphocytes from lamina propria lymphocytes. Intraepithelial lymphocytes are not cytotoxic at six hours, but have a toxic function comparable with lamina propria lymphocytes after 18 hours with all three triggers. Intraepithelial lymphocytes from inflamed mucosa (Crohn's disease and diverticulitis) mediate significantly reduced cytotoxicity in vitro compared with normal mucosa, whereas lamina propria lymphocyte toxicity is not different. Reduced numbers of cytotoxic cells and reduced reactivity to the trigger substances used after in vivo activation or cold target inhibition could explain the observed differences between intraepithelial lymphocytes from inflamed and uninflamed mucosa. Changes in cell mediated cytotoxicity of intraepithelial lymphocytes and lamina propria lymphocytes may be involved in the mucosal damage in these inflammatory conditions.

Die Ätiologie und die Pathogenese der Colitis ulcerosa (CU) und des M. Crohn (MC) sind bisher nicht geklärt, jedoch lassen verschiedene klinische und experimentelle Befunde auf eine Beteiligung des Immunsystems schließen. Es ist seit vielen Jahren bekannt, daß sich bei MC und CU in der Lamina propria der entzündeten Mukosa eine Zunahme der mononukleären Zellen findet. Eine Teilpopulation dieser Zellen enthält zytoplasmatisches oder membrangebundenes Immunglobulin (Übersicht bei [2]). In normaler Darmmukosa überwiegen IgA-positive Zellen. Da das von diesen Zellen produzierte IgA keine oder nur schwache inflammatorische Wirkungen hat, kommt es in der Regel zu einer Immunexklusion ohne Komplement-oder Zellaktivierung. Im Gegensatz dazu wird durch Antikörper der IgG-Klasse eine entzündliche Reaktion unterstützt. Insbesondere die IgG-Subklasse-1 zeichnet sich durch eine ausgeprägte Fähigkeit zur Komplementaktivierung aus, so daß Antikörper dieses Isotyps bei gleicher Antigenspezifität wie IgA möglicherweise eine Entzündung mit Epitheldestruktion auslösen.

Eleven patients with severe Raynaud's syndrome were treated with intravenous infusion of prostacyclin (Prostaglandin I2). Raynaud's syndrome was caused by inflammatory diseases such as progressive systemic sclerosis (N = 9) or thromboangiitis obliterans (N = 2). Five patients had acral ulcerations. Treatment with prostacyclin lead to immediate cessation of acral pain in all patients if doses of 5-6 ng/kg/min were tolerated. In 7 out of 11 patients there was a long-term analgesic effect with clinical improvement of Raynaud's syndrome. In three of five patients we achieved healing of the ulcerations within a few weeks. Plasmaconcentrations of prostaglandin F1-alpha, the main metabolite of prostacyclin, were about 10 times above normal during infusion and returned to normal levels within 30 min after the end of the infusion, in spite of the prolonged clinical effect. Therefore, prostacyclin alone cannot be responsible for the long-term clinical benefit. (Parts of this publication were published as an abstract and presented at the 23rd Congress of the Deutsche Gesellschaft für Rheumatologie (15).

We have examined the concentration of immunoglobulin G (IgG) subclass antibodies in the sera of 27 patients with ulcerative colitis and 21 patients with Crohn's disease as well as in 11 normal controls and 11 patients with systemic lupus erythematosus. In comparison with a control mean serum IgG1 concentration of 5173 micrograms/ml, patients with ulcerative colitis exhibited a significantly increased mean serum concentration of 7924 micrograms/ml (p less than 0.05), whereas patients with Crohn's disease had a near normal mean serum IgG1 level of 5898 micrograms/ml. In contrast, control sera had a mean IgG2 level of 2477 micrograms/ml and ulcerative colitis sera had a similar IgG2 level of 2269 micrograms/ml, whereas Crohn's disease sera had a significantly increased mean IgG2 level of 5111 micrograms/ml (p less than 0.05). Patients with systemic lupus erythematosus, like those with ulcerative colitis, had a markedly elevated serum IgG1 level of 15,594 micrograms/ml (p less than 0.001) without a significantly increased IgG2 serum level (3271 micrograms/ml). Neither ulcerative colitis nor Crohn's disease sera exhibited altered levels of IgG3 or IgG4. These data show that alterations in IgG subclass concentrations occur in the sera of patients with active, untreated inflammatory bowel disease, similar to the previously noted changes in the IgG subclasses secreted by lymphocytes from involved inflammatory bowel disease intestinal specimens.

Serum antibodies cytotoxic to the colon cancer cell line RPMI 4788 were studied in 42 patients with ulcerative colitis, 61 patients with Crohn's disease, 27 patients with other inflammatory diseases (disease-controls) and 22 healthy controls. Cytotoxicity of antibodies towards RPMI 4788 was studied by means of a chromium release assay using peripheral blood mononuclear leucocytes of healthy subjects as effector cells. Using a four hour antibody dependent cell mediated cytotoxicity assay sera from 29% of ulcerative colitis patients contained antibodies cytotoxic for the target, while only 3% of the Crohn's patients and 6% of the disease controls and non of the healthy controls were positive. When an 18 hour assay was applied, however, not only 40% of ulcerative colitis patients, but also 14% of Crohn's patients and 21% of disease controls were found positive. The reactive antibody in the four hour assay was mainly of the IgG class, which points at a classical antibody dependent cell mediated cytotoxicity mechanism. In the 18 hour cytotoxic assay IgG and particularly IgM antibodies were found to be reactive. This suggests that in the latter case other cellular cytotoxic mechanism might be involved. There was a significant inverse correlation between the appearance of the ulcerative colitis restricted IgG-anticolon epithelial cell antibodies (four hour assay) and the disease activity (p less than 0.01). Absorption studies showed that the reactive antigen is not specific for ulcerative colitis colonic tissue, but is similarly found in Crohn's bowel tissue, and to a lower extent in normal bowel, liver and kidney. The reactive antigen, however, could not be detected in brain and lymphoblastoid cells.

51Cr-EDTA activity was measured in urine and blood of patients receiving non-steroidal anti-inflammatory (NSA) drug treatment and of healthy subjects and other patients (controls), after oral intake of 51Cr-EDTA, for the purpose of deciding whether NSA treatment increases urinary excretion of oral 51Cr-EDTA as an expression of increased intestinal permeability. 51Cr-EDTA activity in urine and blood of patients with rheumatoid arthritis (13) being treated with NSA was significantly higher (similar to results in 13 patients with Crohn's disease) than that of a control group (14) of patients with rheumatoid arthritis without such treatment (9) and patients without rheumatic disease (5). Both in patients with rheumatoid arthritis receiving NSA drugs and patients with Crohn's disease there was a highly significant correlation between urinary and blood activity. There was no effect of NSA drugs on renal function. The results indicate that NSA drugs increase interenterocytic permeability to an extent comparable to permeability abnormalities in Crohn's disease.

Twenty-eight patients with chronic polyarthritis, II patients with ankylosing spondylitis and II patients with incipient chronic polyarthritis were examined clinically, by electrocardiography, two-dimensional and TM echocardiography for cardiac involvement. Immunological investigations included determination of homologous and heterologous antimyolemmal (AMLAs), antifibrillary (AFAs) and antinuclear (ANAs) antibodies. Patients with cardiac involvement demonstrated homologous and heterologous antimyolemmal antibodies against the cardiac membrane, particularly of the IgM subclass. AMLAs of high titre were not found in patients with rheumatic diseases without cardiac involvement.

51Cr-EDTA activity was measured in urine and blood of patients receiving non-steroidal anti-inflammatory (NSA) drug treatment and of healthy subjects and other patients (controls), after oral intake of 51Cr-EDTA, for the purpose of deciding whether NSA treatment increases urinary excretion of oral 51Cr-EDTA as an expression of increased intestinal permeability. 51Cr-EDTA activity in urine and blood of patients with rheumatoid arthritis (13) being treated with NSA was significantly higher (similar to results in 13 patients with Crohn's disease) than that of a control group (14) of patients with rheumatoid arthritis without such treatment (9) and patients without rheumatic disease (5). Both in patients with rheumatoid arthritis receiving NSA drugs and patients with Crohn's disease there was a highly significant correlation between urinary and blood activity. There was no effect of NSA drugs on renal function. The results indicate that NSA drugs increase interenterocytic permeability to an extent comparable to permeability abnormalities in Crohn's disease.