In 68 patients with chronic renal failure (CRF), 15 patients with duodenal ulcer and 15 normal subjects, basal plasma gastrin levels and basal and stimulated gastric acid secretion were measured. Two antisera were used: antiserum R2702 with specificity for human G34 and its N-terminal fragments [G34(l-15)] and antiserum 2604 with specificity for the four main components of gastrin (total gastrin). Basal gastrin concentrations of both total gastrin and G34-like immunoreactivity (G34LI) were significantly higher in the CRF patients than in the other two groups, irrespective of dialysis. Total gastrin levels were not correlated with serum creatinine levels. Total gastrin levels were significantly decreased during hemodialyis, but G34LI levels showed no significant change. A small amount of total gastrin was detected in the dialysate by antiserum 2604. As to the postprandial gastrin release, in the first 30 min, the pattern of response in the pateints with CRF was similar to that of the normal subjects, but the peak value was attained later, and the response was more rather prolonged. Gastric analysis showd a low basal acid out put and impaired acid secretion in response to secretagogue. It is concluded that (1) one of the predominant circulating forms of gastrin in CRF is G34LI, and (2) the hypergastrinemia in the CRF patients is probably due to reduced removal of gastrin by kidneys, increased gastrin production by impairment of the negative acid feedback mechanism induced by parietal cell dysfunction or reduced parietal cell sensitivity to gastrin by atrophic gastritis.

A snbclone (clone 20) of chemically induced, marine colon adcnocarcinoma with a potent ability to induce cachexia and another subclone (clone 5) without such an activity were transplanted to syngeneic mice (CDFi) and their tissue weights, blood components and cytokine levels in sera were compared. Mice transplanted with clone 20 showed a profound body‐weight loss by 15 days after inoculation when the tumor accounted for less than 1% of the body weight, along with marked reduction of food and water intakes. Thereafter, they transiently gained in body weight with restoration of food and water intakes. Thus, the change in body weight was biphasic and not proportional to the tumor size. Body fat was lost preferentially, accompanied with a decrease in plasma triglyceride levels. The thymus contracted remarkably, and the peripheral lymphocyte count decreased extensively. Mice transplanted with clone 5, in contrast, did not show any of these changes characteristic of cachexia. Serum concentration of interleukin‐6, which has been proposed as the principal inducer of cachexia in mice with colon 26, increased in mice with clone 5 to levels comparable to those in mice with clone 20. The changes in mice hearing clone 20 could not all be explained in terms of known biological activities of interleukin‐6. Additional unknown factors, therefore, are presumed to contribute to cachexia in mice with clone 20. Identification of them should be helpful in the care of cachectic patients.

In order to further clarify the role of interleukin 6 (IL-6) in the pathogenesis of cachexia, recombinant human IL-6 (hIL-6) was administered s.c. by osmotic pump for 9 days at a dose of 1 or 10 micrograms/day into CDF1 mice inoculated with a non-cachexia-inducing subclone of colon 26 adenocarcinoma (clone 5), or with a cachexia-inducing subclone (clone 20) of this malignancy. The serum level of IL-6 in non-cachectic mice with clone-5 tumors was 35% lower than in cachectic mice bearing clone 20 of colon 26 adenocarcinoma on the 19th day after tumor inoculation. IL-6 administration induced anemia, thrombocytosis and visceral organ hypertrophy not only in mice with clone-5 tumors but also in control mice with no tumor burden. Lipolysis and proteolysis became conspicuous when a large dose (10 micrograms/day) of IL-6 was infused into mice with clone-5 tumors. However, IL-6 supplementation did not induce loss of body weight, a decline in food intake or lymphocytopenia, which were characteristically observed in cachectic mice with clone-20 tumors. In conclusion, IL-6 appears to be a permissive factor for the development of cachexia but, while it can induce some of the symptoms typical of cachexia, it cannot in itself induce the full cachectic syndrome.

In the present study, we examined the immunosuppressive effect of a new drug, FTY 720, on small bowel transplantation (SBT) in rats. Grafts from (LEW x BN) F 1-to-LEW rats treated with FTY 720 at 0.5 mg/kg from day 0 to 14 post-SBT survived significantly longer than untreated grafts. In addition, the administration of FTY 720 combined with cyclosporin (CyA; 5 mg/kg per day) had a synergistic effect on allograft survival. The graft-versus-host reaction (GVHR) that occurred in the LEWto-F 1 rats was markedly reduced after the administration of FTY 720. FTY 720 combined with a low dose of CyA completely abrogated GVHR without any adverse reaction. FTY 720 treatment resulted in a significant decrease in the number of lymphocytes in the peripheral blood and the spleen, but the number of peripheral neutrophils was unchanged. Thus, FTY 720 would appear to be an ideal drug to combine with CyA in order to control the immune reaction after SBT.

No abstract