Comparative sequence analysis of the human T cell receptor beta chain in juvenile rheumatoid arthritis and juvenile spondylarthropathies: evidence for antigenic selection of T cells in the synovium

OBJECTIVE: To identify features of the T cell receptors (TCRs) present on clonally expanded T cells in the joints of patients with similar types of childhood rheumatic disease. Vbeta8 and Vbeta20 TCRs were selected as prototypic for polyarticular juvenile rheumatoid arthritis (JRA) and pauciarticular/juvenile spondylarthropathy (SpA), respectively. METHODS: The portion of the TCR beta chain involved in antigen recognition in the synovial tissue, synovial fluid, and peripheral blood from patients with JRA and juvenile SpA was cloned and sequenced. The frequency of expanded clonotypes, size of expansions, the Jbeta region, and sequence motifs were determined for >2,000 sequences. RESULTS: The majority of Vbeta20 and Vbeta8 clonal expansions were found in the joint rather than the peripheral blood. While instances of both Vbeta8 and Vbeta20 clonal expansion were detected in all disease types, the features of these expanded clonotypes were specific for disease type and Vbeta family. For example, Vbeta20 clonal expansion was characterized by many small expanded clonotypes in samples from patients with pauciarticular JRA and juvenile SpA while single large Vbeta8-specific expansions were found only in patients with polyarticular disease. Motifs specific to individual patients were identified, and for Vbeta20 clonotypes, a motif was found in synovial tissue samples. CONCLUSION: Identification of common TCR features in oligoclonal expansions within individual patients and between patients with the same type of JRA suggests the recognition of a common or limited group of antigens in these diseases.     

HLA B27 and respiratory involvement in axial spondylarthropathies. A retrospective study in 107 male patients

OBJECTIVE: To conduct a retrospective study of respiratory involvement in axial spondylarthropathies according to HLA B27 status. METHOD: Sch?ber's index, chest expansion and lung function parameters were measured in 107 male inpatients with spondylarthropathies, including 78 with and 29 without the HLA B27 antigen (groups I and II, respectively). Active or severe spondylarthropathy was defined based on widely used clinical and laboratory test parameters. RESULTS: The two groups were similar regarding age, body mass index, disease duration, proportion of smokers and proportion of patients requiring nonsteroidal antiinflammatory drug therapy. Overall, 30 patients had pure active disease, 11 had pure severe disease, 26 had active severe disease and 40 had nonactive nonsevere disease. Group I patients were significantly more likely to have active severe disease than group II patients, whereas the opposite was true for nonactive nonsevere disease. Mean erythrocyte sedimentation rate was higher in group I (22.6 +/- 21.6) than in group II (13.3 +/- 12.5) (P = 0.039). Group I patients had lower values for chest expansion (5.4 +/- 2.2 cm versus 6.37 +/- 1.9 cm; P = 0.045), vital capacity (91.9% +/- 13.9% versus 99.5% +/- 17.6%; P = 0.021), and total capacity (91.8 +/- 12.3 versus 98.1 +/- 13.9; P = 0.025). A restrictive defect was found in 12 group I patients versus one group II patient (nonsignificant difference). All patients with restrictive defects had active and/or severe disease. Two-way analysis of variance and Fisher's PSLD post-test suggested that lung function was influenced by disease severity but not by disease activity. CONCLUSION: Lung function impairment may be more common and more severe in HLA B27-positive than in HLA B27-negative spondylarthropathy patients. This difference may be entirely ascribable to increased disease severity in HLA B27-positive patients.     

2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

OBJECTIVE: Bacteria are considered to be important in the pathogenesis of several forms of arthritis. The goal of this study was to apply the 16S ribosomal RNA (rRNA)-polymerase chain reaction method for the detection of bacterial DNA in synovial fluid (SF) and synovial tissue (ST) from inflamed joints. METHODS: Samples from 5 patients with septic arthritis and from 7 with osteoarthritis or arthritis secondary to joint trauma were used as controls. Samples from 6 patients with spondylarthropathy (SpA) and from 20 with undifferentiated arthritis (UA) were analyzed for the presence of bacterial DNA using universal 16S rRNA primers. Automated sequencing and comparative data analysis were performed to identify the species. RESULTS: In the positive control group, the bacterial species cultured from the synovium could be identified in all cases. No bacterial DNA was detected in the SF and ST from patients in the negative control group. In 4 of 6 patients with SpA and 7 of 20 with UA, the analysis of joint samples revealed the presence of bacterial DNA. Sequence analysis indicated the presence of multiple species, which was confirmed by sequencing of cloned products. CONCLUSION: When the the above techniques were used with a stringent regimen, we were able to demonstrate that it is possible to collect and analyze joint samples without contaminating bacterial DNA. The accumulation of phagocytic cells that contain bacterial DNA of various species could play a role in the pathogenesis of both SpA and UA.     

Validation of the European Spondylarthropathy Study Group and B. Amor criteria for spondylarthropathies in Lebanon

OBJECTIVES: 1) To validate European Spondylarthropathy Study Group (ESSG) and B. Amor's criteria for spondylarthropathies in Lebanon. 2) To evaluate the frequency of spondylarthropathies in rheumatological practice in Lebanon. PATIENTS AND METHODS: Cases of definite and probable spondylarthropathy were diagnosed based on the clinical judgement of participating rheumatologists, without reference to the two criteria sets under study. The first two patients without spondylarthropathy seen after each spondylarthropathy case were included into the control group. Criteria in the ESSG and B. Amor sets were looked for in the patient and control groups. The frequency of spondylarthropathy meeting each criteria set was determined. RESULTS: Of the 841 patients evaluated during the study period, 68 met B. Amor's criteria and 72 met ESSG criteria. There were 29 cases of ankylosing spondylitis (40.3%), ten of peripheral psoriatic arthritis (13.8%), two of reactive arthritis (2.8%), two of enteropathic arthropathy (2.8%), and 29 of undifferentiated spondylarthropathy (40.3%). In the definite spondylarthropathy group, sensitivity and specificity were 77.19% and 97.55% for B. Amor's criteria versus 91.23% and 100% for ESSG criteria. The frequency of spondylarthropathy was 8.1% (95% confidence interval [CI], 6.3-9.9) or 8.56% (CI 6.6-10.5) according to B. Amor and ESSG criteria, respectively. CONCLUSION: Our data validate both criteria sets in the Lebanese population, demonstrating that they are useful in populations that are genetically different from the European populations used to develop them. Spondyloarthropathy is the most common in our rheumatology practice.     

Serogroup conversion of Vibrio cholerae

The aim was to analyse the abdominal scintigraphy pattern in patients with seronegative spondylarthropathy (SSp), ulcerative colitis (UC) and Crohn's disease (CD). A total of 117 patients with defined histological lesions of inflammatory bowel disease (IBD) (68 UC and 49 CD), 32 patients with active SSp [European Spondylarthropathy Study Group (ESSG) 1991 criteria] without clinical evidence of IBD and 21 controls without IBD or SSp were studied. All patients with SSp and controls received similar doses of non-steroidal anti-inflammatory drugs. Abdominal scintigraphy images were obtained at 30 and 120 min after injection of 99m-technetium hexamethyl propylene amine oxime (99mTc-HMPAO)-labelled leucocytes. The 99mTc-HMPAO-labelled leucocyte scan was positive in 17 patients with SSp (53.1%), 45 patients with UC (66.1%) and 33 patients with CD (67.3%). Rectum and sigma involvement was more frequent in patients with UC (68.8%) than in patients with SSp (23.5%) or CD (33.3%) (P < 0.05) [odds ratios (OR): 7.1 and 4.4, respectively]. Terminal ileum involvement was more frequent in patients with CD (63.6%) than in patients with SSp (23.5%) or UC (8.8%) (P < 0.05) (OR: 5.6 and 17.9, respectively). The 99mTc-HMPAO-labelled leucocyte scan shows an increased uptake in patients with SSp without evidence of IBD. Perhaps these patients represent one end of the spectrum of IBD, but rectal and terminal ileum involvement were less frequent in patients with SSp than in patients with UC or CD.     

Bowel inflammation and the spondyloarthropathies

The concept of spondyloarthropathies gathers together a group of chronic diseases in which not only the locomotor system is involved but also other organs, especially the gastrointestinal tract. In humans, ileocolonoscopic studies demonstrated the presence of inflammatory gut lesions in all the diseases in the spondyloarthropathy group; their presence varied in the different diseases between 20% and 70%. The inflammation could be related to specific disease features in the spondyloarthropathies. Further research supports the hypothesis of subclinical inflammatory bowel disease in some patients with spondyloarthropathy, in which the locomotor inflammation was the only clinical manifestation. The link between gut inflammation and arthropathy has also been demonstrated in animal models, notably the human leukocyte antigen B27 transgenic rats. The temporal relationship between activity and severity of colonic involvement and flares of peripheral arthritis directs treatment of choice. For all forms of enterogenic arthropathies, nonsteroidal anti-inflammatory drugs remain the acute treatment form. Caution is in order, however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation.     

Beneficial effect of treatment with a monoclonal anti-tumor necrosis factor-alpha antibody on markers of coagulation and fibrinolysis in patients with active Crohn's disease

Crohn's disease has frequently been associated with coagulation abnormalities, causing intravascular deposition of fibrin and local infarction which can subsequently compromise the gut mucosa. Also, arterial and venous thromboembolic complications of larger vessels appear to be associated with Crohn's disease. Coagulation activation in patients with Crohn's disease could be a result of increased serum and tissue levels of cytokines, as reported. We prospectively studied parameters of coagulation and fibrinolysis in 10 patients with active Crohn's disease, who were subsequently treated with a monoclonal anti-tumor necrosis factor-alpha (TNF) antibody. Ten consecutive patients with active Crohn's disease (CDAI > 150), not responding to a daily dose of at least 20 mg prednisolone, received a single infusion of human/mouse chimeric anti-TNF antibody cA2. All evaluable patients attained complete clinical and endoscopic     

Connective tissue growth factor: a novel regulator of mucosal repair and fibrosis in inflammatory bowel disease?

Inflammatory bowel disease (IBD) is a multifactorial disorder which is characterized by massive damage of the epithelium and the underlying mesenchyme of the intestine. Due to the potent effect of connective tissue growth factor (CTGF) on fibroblast proliferation and connective tissue deposition we speculated about a possible role of this mitogen in IBD. Here we demonstrate a strikingly increased expression of CTGF mRNA in surgical specimens of patients suffering from two forms of IBD, Crohn's disease and ulcerative colitis. In most specimens, the levels of CTGF mRNA correlated with the degree of inflammation as assessed by histological analysis of adjacent tissue samples and by expression analysis of the pro-inflammatory cytokine interleukin-1 beta. However, areas of little inflammation which were characterized by severe fibrosis also revealed high levels of CTGF mRNA. Expression of transforming growth factor beta-1 (TGF-beta 1), the only known inducer of CTGF so far, as well as of the CTGF target genes collagen I alpha 1, fibronectin and integrin alpha 5 revealed a strong correlation with the expression of CTGF. These data suggest a prominent role of CTGF in the repair of mucosal injury in IBD and in the aberrant deposition of extracellular matrix leading to fibrosis and stenosis, one major complication in IBD, especially in Crohn's disease.     

Does reactive arthritis caused by Brucella exist? Apropos of 4 cases

OBJECTIVES: Arthritis observed in patients with Brucella infection is usually considered to result from live micro-organisms invading the synovia. We observed four cases of brucellosis in which the clinical and laboratory findings suggested a different mechanism: reactive arthritis. CLINICAL OBSERVATIONS: The diagnosis of brucellosis was made on the basis of serology tests in 3 patients and blood cultures in 1. All 4 patients presented oligoarthritis. The synovial fluid was sterile in 3. Antibiotics were ineffective in reducing joint pain and inflammation whereas local and systemic anti-inflammatory drugs were effective. Three patients also had other manifestations (sausage-shaped toes, talalgia, sacroiliitis) and fulfilled the diagnostic criteria for spondylarthropathy. All patients were positive for antigen HLA-B27. DISCUSSION: These observations suggest that Brucella should be added to the list of intracellular infectious agents capable of inducing reactive arthritis, despite the lack of all the diagnostic criteria. For some, such as the uretritis or diarrhea observed before joint involvement, it would be difficult to implicate the germ. Brucella serology should be part of the etiology work-up for reactive arthritis in endemic areas.     

Incidence of inflammatory bowel disease in northern France (1988-1990)

There were no data concerning the incidence of inflammatory bowel disease (IBD) in France. The aim of this study was to investigate the incidence of Crohn's disease and ulcerative colitis in northern France. This prospective population based study was realised through the gastroenterologists of the region Nord-Pas de Calais and the Somme Department. Each gastroenterologist referred patients consulting for the first time with clinical symptoms compatible with IBD. Data were collected by an interviewer practitioner present at the gastroenterologist's consulting room. Two independent expert gastroenterologists assessed each case in a blind manner and made a final diagnosis of Crohn's disease, ulcerative colitis, ulcerative proctitis, or unclassifiable chronic colitis. From 1988 to 1990, 1291 cases of IBD were recorded: 674 (52%) Crohn's disease, 466 (36%) ulcerative colitis including 162 proctitis (35%), and 151 (12%) unclassifiable chronic colitis. The mean annual incidence was 4.9 per 100,000 for Crohn's disease and 3.2 for ulcerative colitis. The sex ratio F/M was 1.3 for Crohn's disease and 0.8 for ulcerative colitis. The highest age specific incidence rate for Crohn's disease was between 20 and 29 years: 13.1 for women and 9.8 for men. The highest age specific incidence rate for ulcerative colitis was between 20 and 39 years: 5.5 for women and 6.5 for men. This first French prospective study has shown an incidence rate for Crohn's disease comparable with that seen in north European studies but lower than that seen for ulcerative colitis. These results could be related to the different environmental factors or the genetic background of the population studied, or both.     

Plant mitosis promoting factor disassembles the microtubule preprophase band and accelerates prophase progression in Tradescantia

The term spondyloarthropathy (SpA) describes and defines a group of related inflammatory joint disease that share characteristic clinical features and a unique association with the major histocompatibility complex class I molecule HLA-B27. Five subgroups can be differentiated: ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated SpA. The sacroiliac joints are centrally involved in the SpA, most clearly and pathognomonic in ankylosing spondylitis, in which most patients are affected early in the disease. Overcoming some of the diagnostic difficulties of early sacroiliitis, dynamic magnetic resonance imaging was shown to visualize both acute and chronic changes in the sacroiliac joints. The inflammation in the sacroiliac joints in patients with SpA was recently examined in more detail; using immunohistology and in situ hybridrization, T cells, macrophages, and various cytokines were found in infiltrates. Biopsy specimens were obtained under guided computed tomography, and in the same study, intra-articular corticosteroid treatment was successfully undertaken. Further investigation of such biopsy specimens showed the absence of DNA of reactive arthritis-associated bacteria. The pathogenesis of the SpA and the reason for the tropism for the sacroiliac joints is still obscure. The nature of the relation of the genetic background of SpA to initially triggering bacterial infections remains to be established. In chronic disease, autoimmune mechanisms might be more important.     

Immune response and inflammation in Crohn disease. More detailed diagnostics and more specific drugs are soon to be available]

The chronic inflammation in Crohn's disease may be caused by aggressive response to bacterial antigens normal to the gut. Genetic and environmental factors modify the inflammatory response evoked by damage to the mucosal gut barrier. Genetic factors may also determine the subsequent course of chronic inflammation. Further elucidation of the pathogenesis might improve our understanding of the heterogenous nature of Crohn's disease, thus enabling the disease to be subtyped and individualised therapy directed primarily at down-regulation of helper T-cell-1 response to be developed.     

Military history of patients with inflammatory bowel disease: an epidemiological study among U.S. veterans

OBJECTIVES: The military history of patients with inflammatory bowel disease (IBD) contains types of exposure that are not available through other sources and may provide clues about the as-yet unknown etiology of IBD. We therefore sought to describe the epidemiology of IBD among veterans, with particular emphasis on their military history. METHODS: A case-control study compared 10,544 IBD patients and 42,026 controls with respect to age, gender, ethnicity, time period of military service, military duty in Vietnam, status as prisoner of war, and exposure to Agent Orange. RESULTS: Subjects with Crohn's disease were younger than those with ulcerative colitis or without IBD (odds ratio: 0.85; 95% confidence interval [CI]: 0.83-0.87). Both types of IBD affected female veterans significantly more often than male veterans, the relative female predominance being more pronounced in Crohn's disease than ulcerative colitis (0.70; 0.61-0.81 vs 0.83; 0.71-0.96). Whites were more prone to develop both types of IBD than nonwhites (2.46; 2.27-2.68 vs 2.11; 1.95-2.27). Military duty in Vietnam and a status as prisoner of war both exerted a protective influence against Crohn's disease (0.84; 0.75-0.96 and 0.60; 0.41-0.87, respectively), but not ulcerative colitis. CONCLUSIONS: The results are consistent with the hypothesis that exposure to poor sanitation decreases the future risk of developing Crohn's disease.     

Treatment of refractory rapid cycling bipolar disorder with risperidone

BACKGROUND: There is evidence for a hypercoagulable state in inflammatory bowel disease (IBD), and small vessel thrombosis has been identified in the bowel of patients with Crohn's disease, suggesting thrombosis as a possible etiologic factor. Activated protein C (APC) resistance is the most common inherited disorder leading to thrombosis and accounts for 30% to 40% of episodes of idiopathic venous thrombosis. METHODS: The prevalence of APC resistance was studied in 23 patients with IBD (17 with Crohn's disease, 6 with ulcerative colitis) and in 11 control subjects with recurrent abdominal pain or celiac disease, using an APC resistance screening method. RESULTS: One patient with Crohn's disease had a positive screen result, two patients (one with Crohn's, one with ulcerative colitis) had borderline results, and results in all of the control subjects were normal. One patient with Crohn's disease had a history of a thromboembolic event but had a normal screen result. CONCLUSIONS: Activated protein C resistance does not seem to play a major role in the etiology of the hypercoagulable state in inflammatory bowel disease.     

Unconventional imaging techniques in inflammatory bowel diseases

In patients with inflammatory bowel disease (IBD), radiologic examinations are important for diagnosis and treatment. With conventional X-ray examinations, mucosal abnormalities, ulcers and fistulas can be visualised, but no information on the extramural extension of the disease can be obtained. Newer radiologic modalities (ultrasound, CT and MRI) offer new diagnostic possibilities. With ultrasound IBD can be diagnosed with good confidence and it can differentiate between Crohn's disease and ulcerative colitis. CT and MRI are indicated not so much to diagnose the disease but rather to determine the severity and spread of disease activity (transmural and extramural inflammation) and to detect complications such as fistulas and abscesses.     

Use of technetium-tagged white blood cells in patients with Crohn's disease and ulcerative colitis: is differential diagnosis possible?

BACKGROUND: Studies have suggested that scans with technetium-tagged white blood cells (WBC-Tc99m) may be equal to endoscopy in the assessment of extent and activity of inflammatory bowel disease (IBD). OBJECTIVE: We have retrospectively examined the accuracy of WBC-Tc99m scans in differentiating continuous from discontinuous colitis in pediatric IBD. MATERIALS AND METHODS: There were 207 children in the study (96 boys, 111 girls, median age 13 years). This included 29 controls - children with no gastrointestinal disease (NL) who underwent WBC-Tc99m scans for other medical problems. Scans were obtained at 30 minutes and 2-4 hours following injection. Scans were interpreted as showing continuous colitis, discontinuous colitis, or no colitis. RESULTS: In the 77 children with active Crohn's disease (CD) of the colon, the scans revealed discontinuous uptake in 63 children and continuous uptake in 14. In the 29 children with ulcerative colitis (UC), 23 scans showed continuous uptake and 6 revealed discontinuous uptake. Two of these 6 showed focal activity near the appendix, and subclinical appendicitis could not be excluded. Another child was bleeding and the scan could have been misinterpreted as showing small- bowel inflammation. In the last three patients, skip areas were clearly identifiable. In none of these last three patients were the biopsies typical of CD (i. e., no granuloma was identified) nor was inflammation patchy. In summary, of the 106 scans showing inflammation, 6 were classified into the wrong group. CONCLUSION: These data show that WBC-Tc99m scanning can be useful in distinguishing discontinuous from continuous colitis.     

Hepatobiliary complications of idiopathic intestinal inflammations

Extraintestinal manifestations and metabolic complications are very frequent in patients with idiopathic inflammations of the gut and are encountered in at least 35% of these patients. In Crohn's disease extraintestinal manifestations are more frequent than in ulcerative colitis, in particular when the large bowel is affected. Metabolic complications are the result of inflammatory changes of the small intestine or develop as a result of the reduced reabsorption surface of the gut. As to the relationship to the activity of the idiopathic inflammation of the gut, extraintestinal manifestations can be differentiated into those which depend on the activity of the basic disease and those which lack this dependence. From the aspect of a long-term prognosis extraintestinal manifestation independent on the activity of the inflammation of the gut are much more serious, because as a rule they have a long-term and usually progressive trend. The most serious extraintestinal complication is primary sclerotizing cholangitis which in the majority of patients leads to destruction of the biliary pathways and the development of biliary cirrhosis. Depending on the predominantly affected site of the biliary system, primary sclerotizing cholangitis is divided into three types. It is encountered much more frequently in ulcerative colitis than in Crohn's disease. Treatment of primary sclerotizing cholangitis is not very effective. At present it appears that the only drug with an effect on the course of the disease is long-term administration of urodesoxycholic acid. For patients with manifestations of hepatic insufficiency the only solution is transplantation of the liver. In all patients where the diagnosis of primary sclerotizing cholangitis was established, at the same time the possibility of inclusion in a transplantation programme should be considered. The relationship between sclerotizing cholangitis and pericholangitis has not been resolved conclusively. At present the majority of authors is inclined to believe that pericholangitis is part of changes associated with sclerotizing cholangitis. Other hepatobiliary complications of idiopathic inflammations of the gut such as cholelithiasis and parenchymatous liver damage, steatosis of the liver and chronic autoimmune hepatitis are not such a serious problem as sclerotizing cholangitis.     

Interleukin-1 receptor antagonist in differential diagnosis of inflammatory bowel diseases

BACKGROUND: Immunoregulatory properties of cytokines may mediate disordered inflammatory events in inflammatory bowel diseases (IBDs). On the basis of data obtained in experimental colitis, the hypothesis has been advanced that in IBD the balance between interleukin-1 (IL-1) and the naturally occurring IL-1 receptor antagonist (IL-1ra) might influence disease expression. OBJECTIVE: We studied the profiles of IL-1ra and acute phase proteins produced by activated macrophages to determine whether the level of IL-1ra in peripheral blood is a marker of disease activity in IBD and a possible differential diagnostic marker. PATIENTS AND METHODS: Levels of IL-1ra, serum neopterin, urinary neopterin, alpha 1-glycoprotein and C-reactive protein (CRP) were measured in 80 patients with ulcerative colitis, Crohn's disease or infectious colitis. RESULTS: Levels of IL-1ra were markedly increased in patients with active ulcerative colitis or active Crohn's disease compared with those in patients with infectious colitis. Patients with active Crohn's disease had significantly higher serum IL-1ra levels than patients with active ulcerative colitis. Moreover, a positive correlation was found between levels of C-reactive protein, alpha 1-glycoprotein, and serum neopterin and the level of IL-1ra in active Crohn's disease but not in active ulcerative colitis, strongly suggesting that the pathogenesis of the two conditions differs. CONCLUSION: Levels of IL-1ra in the peripheral blood of patients with IBD are of clinical relevance, representing a potent marker of disease activity and a possible differential diagnostic marker.     

Esophageal temperature threshold for sweating decreases before ovulation in premenopausal women

BACKGROUND & AIMS: Anti-tumor necrosis factor alpha monoclonal antibody treatment (infliximab) reduces clinical signs and symptoms in patients with Crohn's disease. The effects of infliximab on mucosal histopathologic abnormalities in Crohn's ileocolitis were studied. METHODS: Thirteen patients with steroid-refractory Crohn's disease were treated with a single infusion of infliximab (5-20 mg/kg), and 5 were treated with placebo. Ileal and colonic biopsy specimens of all patients were collected before and 4 weeks after therapy. Severity of inflammation was assessed by a histological score. Immunohistochemical stainings with antibodies against HLA-DR, CD68, tumor necrosis factor alpha, intercellular adhesion molecule 1, lymphocyte function-associated antigen, CD4, CD8, and interleukin 4 were performed. RESULTS: Total histological activity score was reduced significantly in both ileitis and colitis after infliximab. This is caused by a virtual disappearance of the neutrophils and a reduction of mononuclear cells. Mucosal architecture returned to normal in 4 patients at 4 weeks. The number of lamina propria mononuclear cells decreased because of a global reduction of CD4(+) and CD8(+) T lymphocytes and CD68(+) monocytes. Aberrant colonic epithelial HLA-DR expression completely disappeared. The percentage of intercellular adhesion molecule 1 and lymphocyte function-associated antigen 1-expressing and interleukin 4- and tumor necrosis factor-positive lamina propria mononuclear cells sharply decreased. CONCLUSIONS: Infliximab dramatically decreases histological disease activity in Crohn's ileocolitis. Signs of active inflammation nearly disappear accompanied by a profound down-regulation of mucosal inflammatory mediators.