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Стаття присвячена порівняльній характеристиці різних похідних 5-аміносаліцилової кислоти. Дослідження останніх десятиліть змінили уявлення про можливості застосування аміносаліцилатів у терапії різних запальних захворювань кишечника. У зв’язку з невідомою етіологією хвороби Крона та неспецифічного виразкового коліту етіотропної терапії цих захворювань немає. Сутність лікування зводиться до гальмування активності запалення при загостреннях і проведенні курсів протирецидивної терапії. Численні дослідження, проведені протягом останніх 20 років, показали, що основу базисної терапії хронічних неспецифічних запальних захворювань кишечника становлять препарати 5-аміносаліцилової кислоти, або саліцилати. При виборі лікарської форми слід ураховувати відмінності між препаратами месалазину залежно від типу оболонки. Показано, що з точки зору фармакокінетики найбільш ефективними лікарськими формами месалазину для лікування неспецифічного виразкового коліту та хвороби Крона з ураженням товстої кишки є таблетки з кишковорозчинним покриттям, що забезпечує рН-залежне поступове вивільнення 5-аміносаліцилової кислоти на протязі усієї товстої кишки. Наявні на сьогодні на фармацевтичному ринку препарати 5-аміносаліцилової кислоти здатні контролювати перебіг виразкового коліту та хвороби Крона з ураженням товстої кишки в переважної більшості пацієнтів. Застосування препаратів 5-аміносаліцилової кислоти не обмежується терапією неспецифічного виразкового коліту та хвороби Крона. Препарат широко застосовується при інших захворюваннях кишечника, таких як дивертикулярна хвороба товстої кишки, банальні коліти, променеві ураження ободової кишки, а також для лікування такої поширеної хвороби, як синдром подразненого кишечника. Результати дослідження, що було проведено у відділенні захворювань кишечника ДУ «Інститут гастроентерології НАМН України» упродовж 2 років, показали позитивний ефект 20-денного лікування Месаколом неускладненої дивертикулярної хвороби. Месакол у дозі 1600 мг на добу призвів до повного купірування абдомінальної симптоматики у 68,7 % хворих.

Activation of ulcerative colitis with mesalamine has rarely been reported. In case 1, a 34-year-old man was treated with oral mesalamine, resulting in an exacerbation of colitis that rapidly improved with glucocorticoids and mesalamine withdrawal. Oral cromolyn sodium and occasional low-dose prednisone therapy has maintained long-term remission. In case 2, a 28-year-old man receiving prednisone treatment developed chest pain and myalgias 1 week after initiation of mesalamine that resolved on mesalamine withdrawal. A lower dose of mesalamine with continued glucocorticoids resulted in clinical improvement, and both drugs were tapered. Mesalamine sensitivity was documented endoscopically and histologically by evaluating mucosal changes after two mesalamine enemas during a 24-hour period. There was dramatic progression from quiescent disease to active colitis in 24 hours. Mesalamine sensitivity must be included in the differential diagnosis of ulcerative colitis exacerbations. Concurrent steroid therapy can suppress systemic side effects, making the diagnosis even more elusive.

A randomized, placebo-controlled multicenter trial was conducted to evaluate the efficacy and safety of a delayed-release formulation of 5-aminosalicylic acid (5-ASA) (Asacol; GiulianiBracco, Milan, Italy) for prevention of clinical relapse in 125 patients with inactive Crohn's disease. Patients in remission [Crohn's Disease Activity Index (CDAI) less than 150] between 3 months and 2 years were randomly allocated to receive either 800 mg 5-ASA three times daily (n = 64) or placebo (n = 61) for up to 12 months or until relapse of symptoms. Relapse was defined by a CDAI greater than 150, with a minimum increase of 100 points over the baseline value. The cumulative relapse rates were 12% in the 5-ASA group and 22% in the placebo group at 3 months [95% confidence interval (CI) for the difference, -4 to 24]; 28% and 41%, respectively, at 6 months (95% CI, -4 to 30); and 34% and 55%, respectively, at 12 months (95% CI, 3-39; P = 0.02, log rank test). Significant decrease in the risk of relapse was found in patients with ileitis, in those with previous bowel resection and, in those with prolonged prestudy remission. Eight patients (5 on 5-ASA, 3 on placebo) withdrew from the study because of adverse reactions, but no major clinical or laboratory adverse effect was observed. It is concluded that oral 5-ASA coated with Eudragit S (Rohn Pharma GmbH, Wieterstadt, Germany), 2.4 g daily, is safe and seems superior to placebo in preventing or delaying clinical relapse in Crohn's disease, especially in milder cases and in ileal disease.

Forty patients with active ulcerative colitis were randomly assigned to receive either 4 g of oral enterically coated 4-aminosalicylic acid (para-aminosalicylic acid) or placebo. The duration of treatment was 12 weeks. Disease activity was assessed by grading clinical symptoms of blood, mucus, urgency, sigmoidoscopic findings, and degree of histological inflammation in rectal biopsy specimens. At 12 weeks, 11 of 20 patients (55%) who received 4-aminosalicylic acid showed improvement in clinical and sigmoidoscopic variables. In contrast, only 1 of 20 patients (5%) who had received placebo showed improvement (P less than 0.005). Eighteen of the 19 patients in the placebo group who showed no improvement were treated subsequently with open-label 4-aminosalicylic acid. Of the 18, 11 showed clinical and sigmoidoscopic improvement. Patients allergic or intolerant to sulfasalazine with extensive disease were more likely to respond to 4-aminosalicylic acid.

Introduction: Thiopurines are widely used for the treatment of inflammatory bowel disease, but are associated with hepatotoxicity. 5-Aminosalicylic acid (5-ASA) preparations, can influence thiopurine metabolism by inhibiting thiopurine methyl transferase (TPMT) and subsequently reducing the formation of 6-methylmercaptopurine (6-MMP) metabolites. This is of particular interest as 6-MMP metabolites are associated with the development of hepatotoxicity, but it is unknown whether co-administration of 5-ASA with thiopurines reduces hepatotoxicity. Our aim is to clarify whether 5-ASA co-administration has the potential to decrease in vitro thiopurine-induced hepatotoxicity. Methods: Three human hepatoma cell lines (Huh7, HepG2 and HepaRG) were cultured in William's E medium containing 2% dimethyl sulfoxide. Azathioprine (AZA), 6-mercaptopurine (6-MP) or tioguanine (TG) was added in a concentration range from 3.9 to 4000 μM. In separate coadministration experiments, a fixed non toxic dose of 200 μM 5-ASA was used in combination with 3.9 to 4000 μM of thiopurines. Water-soluble tetrazolium salt-1 (WST-1) cytotoxicity assays were conducted after 24, 48 and 72 hours of incubation. Culture medium plus examined drugs were refreshed every 24 hours. Cell survival curves and half maximal inhibitory concentrations (IC50 were obtained from three independent experiments conducted in triplicate. Results: Co-administration of 5-ASA resulted in significant changes of the IC50 in 7 out of 27 (26%) experiments; in 5 out of 27 (19%) a decreased and in 2 out of 27 (7%) an increased cytotoxicity was seen. In HepaRG cells incubated with 6-MP and 5-ASA, the IC50 increased from 679 (95%CI 502 920 μM) to 5704 μM (95% CI 2174 14962 μM) and from 412 μM (95% CI 321 530 μM) to 918 μM (95% CI 753 1118 μM) compared to HepaRG cells incubated only with 6-MP for 48 and 72 hours, respectively. In HepaRG cells and HepG2 cells, IC50 was approximately 60 μM lower (more hepatotoxic) when incubated for 72 hours with the combination of AZA + 5-ASA in comparison to AZA alone. In Huh7 cells, the IC50 was 80 μM higher after 72 hours incubation with AZA + 5ASA compared to AZA alone. Concentration based, TG was the most toxic thiopurine with an IC50 value of 18 μM after 72 hours incubation in HepaRG cells, compared to AZA (266 μM) and 6-MP (412 μM). Conclusion: Addition of a fixed, non toxic dose of 5-ASA to 6MP resulted in a decreased in vitro toxicity in hepatoma cells.

Background 5-aminosalicylate (5-ASA) formulations are approved for treatment andmaintenance of remission in mild-moderate ulcerative colitis (UC). Determination of the colonic distribution of 5-ASA from various formulations is challenging, since estimates depend on 5-ASA measurements in the serum and the urine. A dynamic model of colonic concentrations of 5-ASA after oral pH dependent delayed-release mesalamine, oral pH dependent extended delayed-release MultiMatrixSystem (MMX) mesalamine, 5-ASA enema, foam and suppositories was developed to determine the colonic pharmacokinetics of these agents. Methods Using published data, we created a computer model with STELLA software (isee, Hanover, NH). Colonic 5-ASA in the right, transverse, descending, sigmoid colon, and rectumwere estimated after once daily doses of the above formulations individually and in combination. Simulations of active mild-moderate UC, (defined as 6 bowel movements (BMs)/day), as well as UC in remission, (defined as 1 BM/day), were performed. Gastrointestinal transit times were determined using published literature modified for periods of sleep. Random distributions were used to model variations in colonic emptying. Data obtained was compared using paired Student's T Tests for difference in mean concentrations with SPSS software (IBM, Armonk, NY, USA.) Results Uneven distribution of 5-ASA was seen with both oral preparations. For UC in remission, the highest levels of 5-ASA in the right colon and transverse colon, (p-value < .01), were from oral delayed-release mesalamine (4.8 gm), in the descending colon and sigmoid colon (p-value < .01) from MMX mesalamine (4.8 gm), and from 5-ASA enema (4g) in the rectum (p-value < .01) (table 1). With active UC, sigmoid and rectal levels from both oral preparations were markedly decreased. Sigmoid levels were highest with foam (4g) (p-value < .01), and rectal levels highest with 5-ASA enema (p-value < .01) (table 1). Differences in recto-sigmoid levels of 5-ASA from enemas and suppositories (1.5g) were markedly influenced by time of BM occurrence (figure 1). For UC in remission, increasing MMX mesalamine dose to 4.8 gm daily resulted in the higher sigmoid-rectal levels compared to combination therapy of 2.4g MMX mesalamine (dose approved for maintenance of remission) with 1g/day 5-ASA enema. Conclusions This is the first dynamic model designed to overcome the difficulties of predicting colonic concentrations of oral and rectally administered 5-ASA formulations. The model suggests that compared to oral delayedrelease mesalamine, MMX mesalamine treatment results in higher 5-ASA levels in the left colon. Higher colonic levels of 5-ASA are achieved when insertion of topical 5-ASAs takes place shortly after a bowel movement. Dynamic modeling provides a rationale for further clinical studies to optimize 5-ASA treatment. Table 1: Mean colonic concentrations of 5-Aminosalicylic acid from oral and topical therapies in ulcerative colitis

Background: Cyclooxygenase-2 (COX-2) is a key enzyme that produces prostaglandin E2 (PGE2) and plays an important role in colorectal tumor growth. Several studies showed that COX-2 inhibiting medications are useful for prevention of colorectal cancer (CRC), however, due to possible adverse events, these medications are not routinely recommended for the prevention. In addition to inhibition of COX-2 activity, recent focus is on 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades PGE2, as another mechanism to regulate PGE2. Some studies reported that 5-aminosalicylic acid (5-ASA), the most widely used antiinflammatory medication for inflammatory bowel diseases with demonstrated long term safety, is associated with reduction in risk of CRC, but the mechanism of action is still unclear. To explore the potential of 5-ASA as a safe preventive agent for CRC, we determined the effect of 5-ASA on COX-2 and 15-PGDH expression. We also investigated the preventive effect of 5-ASA in c-Ha-ras transgenic mice. Materials and Methods: To examine whether 5-ASA affects the expression of COX-2 and 15-PGDH, HT29 cells were cultured in the absence or presence of 5-ASA. To investigate the preventive effect of 5-ASA In Vivo, we used c-Ha-ras transgenic mice, which highly mimics human sporadic colorectal tumor development following injection of 1,2dihydrochloride. The transgenic mice were randomized to Ras or Ras+5ASA group. Mice assigned to the Ras+5-ASA group were treated orally with 5-ASA. The dose of 5-ASA used in the experiments were chosen carefully to reflect efficacy and safety for use in humans. Total protein was extracted from HT-29 cells and from murine colons after excluding sites of tumors and Western blotting analysis was performed for on COX-2 and 15-PGDH. The expression of these proteins were quantified and normalized by beta-actin expression. We examined the number and size of tumors in colon specimens, and performed histopathological analysis and immunohistochemistry. Result: 5-ASA significantly suppressed COX-2 and induced 15-PGDH expression in HT29 cells. In the transgenic mice, we confirmed that tumors in this model were sporadic and there was no inflammation in background mucosa and detected strong expression of COX2 in tumor lesions. The expression of 15-PGDH was remarkably weak regardless of colonic area. Oral 5-ASA intake reduced incidence of colorectal tumor formation from 83% to 40% (P = 0.048) and tumor size from 1.9 ± 1.1mm to 1.1 ± 0.2mm (P = 0.015). Furthermore, we observed down-regulation of COX-2 (P = 0.017) and up-regulation of 15-PGDH (P = 0.048) in the colons. Conclusion: We provide evidence that 5-ASA exerts a chemopreventive effect against colorectal tumor development in c-Ha-ras transgenic mice through mediation of COX-2 and 15-PGDH expression.

Background: Oral 5-aminosalicylic acid (5-ASA) has proven an effective maintenance therapy of ulcerative colitis and may also be useful in Crohn's disease, but its safety in pregnancy has not been established. The present study therefore examined the course and outcome of pregnancies in patients with inflammatory bowel disease who continued to take oral 5-ASA. Methods: Ten patients with ulcerative colitis and 7 patients with Crohn's disease with a total of 19 pregnancies were studied while they were receiving 5-ASA. All patients were previously in remission on 5-ASA, at a mean dose of 1.7 g/day (range, 0.8–2.4 g/day). They continued taking the drug without a change in dose and were followed up throughout their pregnancies and postpartum. Results: Eighteen pregnancies resulted in full-term delivery. No fetal abnormalities were found at delivery, and there were no clinical or biochemical abnormalities in the neonatal period. Four patients had a relapse. One patient required a colectomy but carried on to a full-term pregnancy. One patient had a miscarriage, but she had miscarried on four previous occasions before taking 5-ASA. She subsequently had a successful pregnancy on 5-ASA. Conclusions: Oral 5-ASA appears to be safe for the management of inflammatory bowel disease during pregnancy.

Background: The efficacy of the leukocyte recruitment inhibitor, N -[9 H -(2,7-dimethylfluoren-9-ylmethoxy)carbonyl]-l-leucine (NPC 15669) was compared with drugs used to treat inflammatory bowel diseases in a rat model, acetic acid-induced colitis. Methods: Colonic damage assessed by visual inspection, histological quantitation of tissue injury, vascular permeability, myeloperoxidase (MPO) accumulation, and synthesis of inflammatory mediators were measured. Results: Intrarectal pretreatment with NPC 15669 results in a significant reduction of all measured indices of inflammation. The median effective dose (ED 50 ) of NPC 15669 for inhibition of MPO accumulation and vascular permeability is 13.2 mg/kg and 31 mg/kg, respectively. The active moiety of sulfasalazine, 5-aminosalicylic acid (5-ASA), the antioxidant/5-lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA) and the corticosteroids dexamethasone and hydrocortisone, yielded ED 50 values (MPO accumulation) of 68 mg/kg, 95 mg/kg, 0.7 mg/kg, and 13 mg/kg, respectively. When formulated suspensions of NPC 15669, 5-ASA, or dexamethasone were used, potency was increased 10–40-fold. Furthermore, NPC 15669 (10 mg/kg) administered 7 hours after acetic acid and evaluated 24 hours after acetic acid administration significantly attenuated neutrophil influx (70% inhibition of MPO accumulation), whereas 5-ASA (100 mg/kg) displayed no therapeutic effects. Conclusions: NPC 15669 may be useful in the treatment of inflammatory disorders.

Purpose: Basiliximab (BSX) is a chimeric monoclonal antibody that binds with high affinity to CD25, thereby inhibiting IL-2 binding, and IL-2 mediated proliferation of lymphocytes. Evidence suggests that IL-2 plays a role in the development of steroid-resistant T lymphocytes, and an open label study of BSX in steroid-resistant ulcerative colitis (UC) suggested benefits in reduced disease activity and steroid dose. We sought to determine the efficacy and safety of BSX in steroid-refractory UC. Methods: Adults with moderate to severe (Mayo score ≥6 and endoscopic subscore ≥2) UC extending above the rectum despite at least 14 days of oral prednisone (PRED) 40 to 50 mg/d prior to study entry. Concomitant 5ASA, 6MP/AZA were permitted with stable doses. Subjects with systemic features of toxicity, or who had received infliximab or cyclosporine within 3 months, or IV steroids or rectally administered medications within 2 weeks, were excluded. The first 135 subjects were randomized 1:1:1 to blinded BSX 40 mg, 20 mg, or placebo (PBO) IV at weeks 0, 2, 4. An additional 14 subjects were randomized to BSX 40 mg or placebo groups after the first 135 subjects were enrolled. All subjects received PRED 30 mg/d po from day 0 to week 2, then tapered by 5 mg weekly to 20 mg/d, and maintained this dose till week 8. The primary analysis was a comparison of the rate of clinical remission (Mayo score ≤2, no subscore >1) in the BSX 40 mg group compared to PBO at week 8. Secondary analyses compared BSX 20 mg to PBO at week 8, and clinical response (decrease in Mayo score by ≥3) for both groups to PBO at week 8 using Cochran-Mantel-Haenzel test stratified by Mayo Score (≤10, >10), use of 6MP/AZA, and geographic region of study site. Subjects were followed until week 12 for safety. The study had 80% power to detect a difference of 21% assuming PBO clinical remission rate of 19% with a 2-sided alpha of 0.1. Results: A total of 149 subjects were randomized and received at least 1 dose of study drug. Results are shown in the table below. Six subjects (2 in each group) had serious adverse events, including 1 patient assigned to BSX 20 mg who died with disseminated tuberculosis and previously undiagnosed HIV. Forty-five percent of subjects who received BSX developed neutralizing anti-BSX antibodies. Conclusions: Basiliximab was not effective for steroid sensitization and induction of remission in outpatients with steroid-resistant moderate-to-severe UC.

Background: The 6-mercaptopurine (6MP) metabolites, 6-thioguanine (6TG) and 6-methylmercaptopurine (6MMP) have been shown to correlate with therapeutic efficacy and toxicity, respectively, in patients with inflammatory bowel disease (IBD). Recent studies have suggested that 6MP metabolism may be influenced by factors such as drug formulation (6MP vs. azathioprine [AZA]) and concomitant use of 5-aminosalicytic acid (5ASA) agents. Aim: To elucidate the effects of drug formulation and 5ASA use on 6MP metabolism in adult patients with IBD. Methods: We analyzed 99 IBD patients who were on stable doses of 6MP (N =49) or AZA (N=50) for at least 2 months. All patients had 6TG and 6MMP metabolite levels measured. Drug formulation was confirmed by direct or telephone contact. An adjusted dose of 6MP was calculated by multiplying the actual dose by a conversion factor of 2.07 to allow direct comparison to AZA dose. Relationships were analyzed using linear regression of metabolite levels versus drug dose adjusted for drug formulation and 5ASA use. Results: Drug FormulationFor the entire group, drug dose correlated with 6TG (P = 0.007) and 6MMP (P

The release pattern, bioavailability, and kinetics of a 5-aminosalicylic acid tablet with sustained release were studied in humans. Six ileostomy patients received a single dose (500 mg). Eight and 48 h later, respectively, 58% and 65% of the dose was recovered in the ileostomy effluents, either as 5-aminosalicylic acid still retained in the preparation, free 5aminosalicylic acid or acetyl-5-aminosalicylic acid. Fourteen healthy volunteers took 1500 mg of 5aminosalicylic acid per day for 6 days and a steady state plasma acetyl-5-aminosalicylic acid concentration was reached on day 5 (1.1–2.9 μg/ml). 5-Aminosalicylic acid was not detected in the plasma. At steady state, 40% of the 24-h dose was recovered from feces, and 53% from the urine. The sustainedrelease preparation studied provides sufficient amounts of 5-aminosalicylic acid to all parts of the gut and its curative effect in ulcerative colitis and Crohn's disease should be examined in controlled trials.

Azodisalicylate, a second generation drug of sulfasalazine, delivers twice the amount of 5-aminosalicylic acid to the colonic lumen on a molar basis when split by bacterial azoreductases. In 6 patients with inactive ulcerative colitis, the colonic metabolism of sulfasalazine and azodisalicylate was studied by equilibrium in vivo dialysis of feces to measure the therapeutically relevant concentrations of their metabolites (5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid) in free fecal water. After oral intake of sulfasalazine (2 g/day) the total luminal concentrations of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid determined by high-performance liquid chromatography were higher (median 14 mmol/L) than previously reported and almost doubled (median 25 mmol/L, p less than 0.05) when sulfasalazine was replaced by the same dose of azodisalicylate. In contrast, the corresponding serum concentrations were negligible. After administration of azodisalicylate to 12 healthy volunteers, a similar distribution of the metabolites was found. In nearly all cases, the concentrations of azodisalicylate in fecal dialysates were below the detection limit (6 mumol/L). We conclude, therefore, that oral azodisalicylate is a highly effective means of delivery of 5-aminosalicylic acid to the colonic mucosa. In addition, determination of the active metabolites in free fecal water seems important for the interpretation of results obtained in vitro concerning the mode of drug action.

The aim of the present study was to determine whether the split products of sulfasalazine, sulfapyridine, and 5-aminosalicylic acid can ameliorate ischemia/reperfusion-induced injury to the gastric mucosa. Gastric mucosal damage was assessed by measuring (a) 51 Cr-labeled red blood cell leakage into the gastric lumen, (b) the area of gross mucosal lesions, and (c) the extent of histologically demonstrable mucosal damage. In rats treated with 5-aminosalicylic acid, but not in those treated with sulfapyridine, the leakage of 51 Cr-labeled red blood cells and the area of gross mucosal lesions after ischemia/reperfusion were significantly reduced as compared with untreated (control) rats. Inasmuch as 5-aminosalicylic acid (the therapeutic moiety of sulfasalazine) has been reported to be a hydroxyl radical scavenger, we also assessed the effects of dimethylsulfoxide (another hydroxyl radical scavenger) on ischemia/reperfusion-induced gastric mucosal injury. In rats treated with dimethylsulfoxide, leakage of 51 Cr-labeled red blood cells and the area of gross mucosal lesions after ischemia/reperfusion were significantly reduced as compared with control rats. The results of this study support the contention that ischemia/reperfusion-induced gastric bleeding involves the hydroxyl radical and indicate that 5-aminosalicylic acid significantly attentuates this vascular injury.

The efficacy of 5-aminosalicylic acid enemas in maintaining remission in left-sided ulcerative colitis was studied. Twenty-five patients in remission for at least 2 mo were randomized to receive either 1-g 5-aminosalicylic acid or placebo enemas daily and were followed up for 1 yr. Eleven of 13 patients randomized to placebo relapsed after a mean of 16 wk. Nine of 12 patients randomized to 5-aminosalicylic acid remained in remission for 1 yr, 2 others in remission withdrew by request, and 1 relapsed at 10 wk. The difference between relapse rate on 1-g 5-aminosalicylic acid versus placebo was significant (p less than 0.005). Seven patients entered the blinded trial a second time. Three of 4 patients randomized to 5-aminosalicylic acid remained in remission and 1 relapsed. Three randomized to placebo relapsed at a mean of 14 wk. One-gram 5-aminosalicylic acid enemas are safe and effective in maintaining remission in patients with left-sided ulcerative colitis.

Eighteen patients with active Crohn's disease entered an open trial with 5-aminosalicylic acid in a slow-release preparation. All had lesions of the small bowel. Ten of them also had Crohn's disease of the colon. 5-Aminosalicylic acid, 500 mg three times daily, was administered for 6 wk. Even with meticulous monitoring, no side effects of any kind were observed, particularly no cases of renal affection, which could have been expected from animal studies. The clinical course was estimated as improved in 13 patients (72%), unchanged in 2 patients (11%), and aggravated in 3 patients (17%); 2 of these 3 were withdrawn from the study and switched to alternative treatment. The Crohn's disease activity index decreased from a median of 226 points to 99 points. On the basis of these results, large-scale controlled therapeutic trials seem warranted in order to establish clinical evidence for the benefit of peroral treatment with 5-aminosalicylic acid in patients with Crohn's disease.

We have examined the effects of sulfasalazine and its metabolites sulfapyridine and 5-aminosalicylic acid on antibody secretion by normal peripheral blood and intestinal mononuclear cells. Sulfasalazine and 5-aminosalicylic acid both inhibited pokeweed mitogen-stimulated secretion of immunoglobulins (Igs) A, G, and M by peripheral blood mononuclear cells in a dose-dependent manner, whereas sulfapyridine had little effect. Sulfasalazine and 5-aminosalicylic acid also inhibited spontaneous secretion of IgA by intestinal mononuclear cells, but sulfapyridine did not. Sulfasalazine inhibited pokeweed mitogen-stimulated lymphocyte proliferation, while 5-aminosalicylic acid and sulfapyridine exhibited minimal inhibition. Sulfasalazine was toxic for peripheral blood mononuclear cells, whereas 5-aminosalicylic acid and sulfapyridine were not toxic. Thus, the inhibition of antibody secretion by sulfasalazine was due to direct toxicity. On the other hand, 5-aminosalicylic acid, the therapeutically active component of sulfasalazine, was neither toxic nor antiproliferative, and appeared to exert its effects on metabolic pathways directly related to antibody synthesis. The calculated ID 50 values of 5-aminosalicylic acid for antibody secretion were 1.35 mM for IgA and 1.05 mM for IgG, concentrations that are achieved in the colons of treated individuals. Indomethacin did not inhibit antibody secretion at pharmacologically relevant concentrations. 5-Aminosalicylic acid mediated inhibition of antibody secretion may play a role in inflammatory bowel disease by stopping antibodymediated memory events involved in the induction or perpetuation of the disease process.