Elisabetta Bertinelli

Mucosal concentrations of interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-α in pelvic ileal pouches

Concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were determined by solid-phase ELISA in tissue homogenates of mucosal biopsy specimens obtained from pelvic ileal pouches in 13 patients with pouchitis (reservoir ileitis) and 17 with pouches without pouchitis. Normal ileal mucosa was used as a control. IL-1β was detected in all tissue homogenates from patients with pouchitis compared with only 29% from pouches without pouchitis and none from controls. IL-6 and IL-8 were present in all pouchitis specimens, in 70% of the specimens from nonpouchitis and only 30% of specimens from controls. TNF-α was undetectable in all specimens examined. The concentrations of IL-1β, IL-6, and IL-8 were significantly greater (P<0.001) in biopsy specimens from pouchitis compared to those from pouches without pouchitis or normal ileal mucosa and in patients with pouchitis tissue levels of IL-1β significantly correlated with IL-6 (P<0.05) and IL-8 (P<0.01). Furthermore IL-1 and IL-8 levels were significantly higher in tissue specimens from nonpouchitis pouches than in those from normal ileal mucosa (P<0.02). These results suggest that an enhanced cellular immunity operatesin vivo at the mucosal level in pouchitis as in the case of ulcerative colitis.

Influence of steroid treatment's duration in patients with active Crohn's disease

Steroids are very useful drugs in the treatment of active Crohns disease (CD), but clinical relapses after steroid withdrawal may be very high.We investigated the efficacy of two steroid regimens of different duration in inducing remission and in maintaining it after drug suspension.Patients with active CD were randomly assigned to scheme A, lasting 7 weeks (27 patients), or to scheme B, lasting 15 weeks (27 patients). Remission rates at the end of the treatment were 81% for scheme A and 85% for scheme B. Relapse rates at 6 months after stopping the treatment were 50% (11 patients) and 52% (12 patients), respectively.Remission rates seem not to be influenced by the duration of the treatment, but patients recently treated with steroids showed a higher relapse rate if they received the short-duration treatment.

Respiratory burst of circulating polymorphonuclear leukocytes and plasma elastase levels in patients with inflammatory bowel disease in remission

The activation of circulating polymorphonuclear leukocytes was determined in terms of superoxide radical generation and granulocyte elastase release in untreated patients with ulcerative colitis (N=10) and Crohns disease (N=9) in remission and in control subjects (N=10). Superoxide radical generation was determined by monitoring spectro-photometrically the reduction of ferricytochrome, after stimulation of cells with phorbol myristate acetate. Plasma elastase concentration was measured by a solid-phase enzyme immunoassay technique as the complex with alpha-1-proteinase inhibitor. Superoxide formation by polymorphonuclear leukocytes from patients with ulcerative colitis and Crohns disease was significantly lower compared with controls [median (range) nmol/min/mg protein: Crohns disease 7.8 (7.1–9.6); ulcerative colitis 8.25 (7.4–10.3); controls 14.7 (13.6–15.8)] (P < 0.001), while no difference was found between the two groups of patients. In contrast plasma elastase levels in patients with ulcerative colitis and Crohns disease were similar to that of controls. This defective respiratory burst of polymorphonuclear leukocytes in patients with inflammatory bowel disease in remission, in absence of an altered degranulation, could represent an important factor for the pathogenesis of these diseases.

Interleukin 1β (IL-1β) release from fresh and cultured colonic mucosa in patients with ulcerative colitis (UC)

Interleukin-1, a cytokine produced by macrophages and other tissue cells, has a major role in inflammatory and immunological responses. Increased levels of IL-1 activity have been reported in experimental colitis and in patients with active Crohns disease (CD) and ulcerative colitis (UC). IL-1β release from fresh and cultured colonic biopsies and IL-1β plasma concentrations was determined in 15 patients with active UC, 16 with UC in remission and 10 normal control subjects. Biopsies, taken at colonoscopy were weighed, washed in 1 ml of 0.9% sodium chloride solution and then cultured for 24 h in 10% fetal calf serum/RPMI. IL-1β activity was determined by ELISA KIT (Cystron Biotechnology) in plasma samples, washing solution and the incubation medium. Very low levels of IL-1β were detected only in 3 plasma samples, all from active patients. Significantly more IL-1β was released from fresh and cultured colonic mucosa obtained from patients with UC in remission compared to normal mucosa (p<0.01). Furthermore, specimens from active UC released significantly more IL-1β than those from patients in remission (p<0.01). In conclusion, IL-1 may play an important role in mediating the inflammatory response in UC.

Macrophage subpopulations in pouchitis.

SIR,-The leading article that appeared in Gut raised the question of whether inflammatory bowel diseases (IBD) are autoimmune disorders. Since IBD do not fulfil all criteria for classification as autoimmune disorders, analogies between the two groups of diseases may be of interest. Circulating interferon (IFN) is commonly detected in patients with autoimmune disorders (the so called autoimmune-IFN) as well as in patients with AIDS, correlating with disease progression.2 Although circulating IFN is not included in the list of criteria suggestive of autoimmune disorders, the presence of acid-labile IFN-a is believed to reflect continuing autoimmune reactions.We tested 51 sera from patients with either ulcerative colitis or Crohns disease for the presence ofIFN using a sensitive bioassay. For comparison, 41 sera of HIV infected patients were also tested. No IFN was detected in the serum samples from the IBD group while 10 sera from the HIV infected patients were positive for IFN with titres ranging from 5 to 200 IU/ml. This IFN was acid-lable, and characterised as a-type by sensitivity to neutralisation with specific antiserum. IBD sera were also tested for the presence of neutralising antibodies to IFN a or y6 and no IFN antibodies were found in IBD sera. Thus, although T cells and macrophages are activated in Crohns disease and IFN-y is actively released in the diseased gut,7- no circulating autoimmune IFN can be detected in these patients. These observations provide new evidence against an autoimmune aetiology for IBD. FRANCESCO PALLONE Clinica Medica 2, Universita la Sapienza, Viale de Policlinico 00161, Rome, Italy STEFANO FAIS Cattedra di Gastroenterologia, Clinica Medica II, Policlinico Umberto I, Rome, Italy MARIA R CAPOBIANCHI Instituto di Virologia, Universita di Roma, La Sapienza, Rome, Italy