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Lymphoid sub populations in the blood and rectal mucosa were studied in six patients with ulcerative colitis or Cohn's disease who had been treated for over three year with azathioprine. Serial assays were performed to observe the changes occurring up to 12 weeks after treatment with azathioprine was stooped. While the patients were on the drug tow lymphoid populations showed marked depression. These were the plasma cells of the rectal lamina procris, and blood lymphocytes with cytotoxic activity against antibody-sensitized tared cells ('k' cells). After stopping azathioprine, both population showed a rapid rise to reach near normal levels by 12 weeks, Most of the recovery occurred within 3-5 weeks. There was no significant change in circulating immunogolblin-staining cells which could be attributed to the drug. Nor was azathioprine shown to have any effect on the mitotic response of lymphocytes to phytohaemagglutinin. Three patients, however, gave very low or erratic responses to PHA, which may have been related either to their disease or to steroid therapy, These results are discussed in relation to the mode of action of purine analogues as immunosuppressive agents. [ABSTRACT FROM AUTHOR]

Immunogenic molecules are being absorbed continually from the alimentary tract and a substantial proportion of normal people have detectable levels of circulating antibody against soluble food proteins and intestinal bacteria. In our view antibodies to soluble proteins form part of a physiological mechanism for preventing these proteins from entering the systemic circulation. In the absence of antibody the liver failed to remove significant quantities of soluble protein antigen from the portal circulation, but in the animal with sufficient circulating antibody to combine with antigen in optimal proportions, the liver retained 80 per cent of the injected protein. The liver became progressively less efficient for the removal of injected complexes which had been prepared in vitro and contained increasing amounts of antigen in excess of optimal proportions. The consequences of antigen excess, as they relate to inflammatory bowel disease, are discussed. The theoretical consequences of antibody excess are also discussed. [ABSTRACT FROM AUTHOR]

Evidence for circulating immune complexes in sera of patients with ulcerative colitis or Crohn's disease is described. Such sera produced significantly greater inhibition of antibody-induced cytotoxicity mediated by lymphocytes than did sera from normal control subjects. Inhibitory activity of patients' sera showed a positive correlation with severity of disease, the height of the ESR and, in the case of ulcerative colitis, with the severity of inflammation as seen at sigmoidoscopy. Using gel filtration on Sepharose 6B, inhibitory activity was found in fractions of higher molecular weight than monomeric IgG but of lower molecular weight than IgM. These fractions were shown to contain IgG measured by immunodiffusion. Evidence that inhibition is not due to aggregated IgG molecules is provided by the fact that no correlation was found between inhibitory activity and total IgG concentration. A possible role of immune complexes in the pathogenesis of ulcerative colitis and Crohn's disease is proposed. [ABSTRACT FROM AUTHOR]