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Whether inflammatory bowel diseases (IBD) can be classified as autoimmune disorders is not established. Since circulating acid-labile interferon-alpha (IFN-alpha) is believed to reflect autoimmune reactions, we tested sera from two groups of IBD patients for the presence of circulating IFN. No detectable IFN was found in 51 serum samples of IBD patients. Furthermore, in no serum sample of IBD patients were neutralizing anti-IFN antibodies found. In contrast, acid-labile IFN-alpha was present in sera from 21/52 HIV-infected and from 6/14 systemic lupus erythematosus patients. These observations provide evidence that IBD differs from systemic autoimmune disorders, at least for the presence of circulating IFN.

We tested the hypothesis that serum factors present in Crohn's disease interfere with the process of lymphocyte activation. The mitogen-induced proliferation and the expression of early activation antigens by normal lymphocytes cultured in the presence of either Crohn's disease sera or sera from different controls were evaluated. The mitogen-induced proliferation was significantly impaired in the presence of Crohn's disease sera. These sera markedly inhibited the mitogen-induced interleukin-2 receptor (IL-2R) expression (48% inhibition), while the effect of sera on the expression of the transferrin receptor and the 4F2 antigen was much less pronounced. Diafiltration experiments showed that the inhibitory effect was confined to a 30-50-kD serum fraction. Such a serum property was not related to the patients' disease activity and disappeared after surgical removal of the affected bowel. The capability of inhibiting the mitogen-induced IL-2R expression was not restricted to Crohn's disease and was observed with sera from other inflammatory and neoplastic gastrointestinal disorders. This study indicates that a marked inhibition of the IL-2R is a mechanism underlying the immunosuppressive property of the serum in Crohn's disease and in other gastrointestinal conditions.

The colonic epithelial expression of HLA-DR molecules and of other markers of cell membrane perturbation was investigated by immunofluorescence in biopsy specimens from patients with ulcerative colitis and Crohn's disease. It was found that in virtually all specimens from either groups showing active inflammation there was a diffuse epithelial expression of HLA-DR molecules. There was no relation between the grading of active inflammation and the epithelial expression of HLA-DR antigens. The epithelium of virtually all specimens from the macro and microscopically uninvolved areas of patients with active colitis and from patients with histologically quiescent colitis showed no detectable expression of HLA-DR molecules. The counts of isolated lamina propria lymphocytes expressing the transferrin receptor and the interleukin 2 receptor were higher in specimens with HLA-DR+ epithelium than in those with a HLA-DR- epithelium. Twenty-nine of the 35 (83%) HLA-DR positive specimens proved to express the 4F2 antigen on their epithelium and 19 (54%) were positive for the transferrin receptor. All sections positive for either the 4F2 antigen or the transferrin receptor were also HLA-DR positive while all HLA-DR negative sections were also negative for either of the two other markers. Data in this study suggest that in active IBD the epithelial participation in active inflammation is associated with a sequence of cell membrane rearrangements, and that the expression of HLA-DR molecules is a part of this sequence.

Colonic epithelial cells (CEC) were isolated from actively inflamed mucosa of IBD patients and checked for HLA-DR, HLA-DP, and HLA-DQ. Half of the freshly isolated CEC from IBD tissue expressed DR, and one third were positive for DP and DQ. Normal human CEC were then cultured for 24 h and their expression of these markers in response to different types of in vitro stimulation was investigated. A significant increase in the expression of DR, DP and DQ was observed in response to the nonspecific mitogen phytohaemagglutinin (PHA), the lymphokine gamma-interferon (gamma-IFN) and the epidermal growth factor (EGF). The enhancement of DR expression was more marked than that of DP and DQ. The effect of gamma-IFN was more rapid and significantly more marked than that of either PHA and EGF for all three antigens. EGF appeared to be more potent than PHA in enhancing the expression of DP and DQ. The data from this study indicate that HLA-D region antigens can be induced on human CEC by different types of stimuli and provide further evidence that the expression of these markers in the colonic epithelium is a normal event the magnitude of which can increase under various circumstances. The data also suggest that the increased expression of HLA-D region antigens by IBD CEC occurs as a result of different mechanisms, and that this expression is an indicator of the active participation of the colonic epithelium to the mucosal inflammatory response.