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PubMed1992

Interaction of paracrine factors during labour: interleukin-1 beta causes amplification of decidua cell prostaglandin F2 alpha production in response to bradykinin and epidermal growth factor.

Inflammatory mediators have been implicated in the stimulation of decidual prostaglandin (PG) production during infection-driven preterm labour. The aim of the present study is to investigate a potential interaction between interleukin-1 beta (IL-1) and bradykinin (BK) in the regulation of decidual PGF2 alpha production and PG precursor release. Pretreatment of primary decidua cell cultures with IL-1 significantly enhanced PGF2 alpha production in response to BK. This effect was accompanied by an increase in unesterified arachidonic acid and an enhanced turnover of arachidonoyl phosphatidate. Bradykinin also stimulated arachidonic acid release in decidual fibroblasts, an effect which was potentiated in the presence of epidermal growth factor (EGF), but which was not accompanied by an increase in PGF2 alpha production. Decidual fibroblasts pretreated with IL-1 manifest a 10-fold increase in PGF2 alpha production in response to BK and EGF. These observations provide the first description of synergism between cytokine, kinin and growth factor in the uterine decidua which may partly mediate the in vivo increase in prostaglandin production associated with decidual activation and infection-driven labour.

Arachidonic Acid↗

PubMed2006

Mechanisms of disease: Transcription factors in inflammatory arthritis.

Studies on the pathogenesis of inflammatory arthritides have begun to delve into the molecular and cellular mechanisms behind the development of these diseases, and transcription factors, as key regulators of immune-effector-cell development and function, have received growing attention. Their involvement in immune cells, such as T and B lymphocytes, macrophages and neutrophils, and cells from diseased tissues, such as synoviocytes, has been investigated, revealing dominant roles for members of the nuclear factor kappaB family, signal-transducer and activator of transcription family, and activator protein 1 family. This review summarizes recent findings and current knowledge regarding the roles of transcription factors in inflammatory arthritis, as evidenced by both biological and genetic studies, and discusses the relevance of these findings for anti-inflammatory therapies.

Anti-Inflammatory Agents↗

PubMed1991

Latrine ownership as a protective factor in inflammatory trachoma in Egypt.

We investigated the association between inflammatory trachoma in children aged 1-5 and environmental and sociodemographic risk factors in a rural Nile Delta hamlet. Inflammatory trachoma clustered in households, emphasising the child-to-child nature of transmission in the hamlet. Multiple logistic regression analysis revealed three factors predicting inflammatory trachoma in children: the absence of a latrine in the household, school-age siblings with inflammatory trachoma, and additional same-age siblings (with or without disease) in the household. In the Egyptian setting the presence of pit latrines in all houses, even when full and unscreened, might result in a reduction in trachoma prevalence in this population from the current 49% to 35%. The construction of pit latrines may offer the simplest and most acceptable environmental method for reducing trachoma in this trachoma endemic area.

Child, Preschool↗

PubMed2000

Abdominal aortic aneurysm and aortic occlusive disease: a comparison of risk factors and inflammatory response.

OBJECTIVE: to compare patients with abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) with regard to risk factors for atherosclerosis, co-morbid conditions and inflammatory activity. PATIENTS AND METHODS: a total of 155 patients undergoing abdominal aortic surgery between January 1993 and October 1997: 82 (53%) had aneurysmal disease and 73 (47%) had occlusive disease. Principal risk factors were compared: age; gender; smoking; hypertension; hyperlipidaemia; diabetes mellitus; severe peripheral vascular disease (PVD) and ischaemic heart disease. Aortic wall tissue samples were obtained during surgery. A prospective blind analysis was performed for the presence of inflammatory cytokines TNF-alpha, IL-1 beta, IL-6 and TGF-beta. RESULTS: the average age of AAA patients was 74 years (50-88), while that of AOD patients was 61 years (43-82) (p<0.0001). Diabetes mellitus was found to be much more prevalent in the AOD group (p<0.001), while hypertension and severe PVD were more prevalent in the AAA group (p<0.001). No differences were found concerning any of the risk factors. Inflammatory cytokine activity: AAA tissue samples contained significantly higher mean TNF-alpha and IL-6 levels compared to the AOD samples (5.6+/-2.7 x 10 E-4 vs. 4.4+/-2.7 x 10 E-5 atmoles/microl (p=0. 01), and 0.6+/-0.4 vs. 0.01+/-0.006 atmoles/microl (p=0.02) respectively). No differences were found related to IL-1 beta and TGF-beta. CONCLUSIONS: (1) Patients with AAA have fewer atherosclerotic risk factors than do patients with AOD. (2) Patients with AAA and AOD have significantly different inflammatory activity. (3) The data supports the hypothesis that AAA and AOD are probably two different pathological entities.

Adult↗

PubMed1995

Psychosocial factors in inflammatory periodontal diseases. A review.

Reviewing the literature concerning the possible rôle of psychosocial factors in the aetiology of inflammatory periodontal diseases, it may be concluded that there is evidence which strongly suggests that emotional stress is one of the predisposing factors to ANUG. On the other hand, it is not clear that the scientific evidence is sufficient to substantiate the hypothesis that psychosocial factors are of aetiological importance in periodontitis. The proposed mechanisms which may mediate the putative relationship between psychosocial conditions and inflammatory periodontal diseases remain to be tested. However, psychoneuroimmunologic studies make lowered host resistance especially interesting as a possible mechanism. Although available studies do not definitively support causal relationships, they suggest that psychosocial factors may be involved in the aetiology of inflammatory periodontal diseases, which, in turn, would relate to clinical management of these conditions.

Animals↗

PubMed1995

Activation of monocyte effector genes and STAT family transcription factors by inflammatory synovial fluid is independent of interferon gamma.

Activated monocytes play an important role in the pathogenesis of inflammatory arthritis. Blood monocytes which enter the inflamed joint become activated upon adherence to extracellular matrix and exposure to a complex inflammatory environment. We have analyzed the mechanism of monocyte activation by soluble factors present in inflammatory synovial fluid (SF). Greater than 75% of inflammatory SFs tested (a total of 22 fluids to date) increased cell surface expression and dramatically increased mRNA levels of monocyte activation markers Fc gamma RI, Fc gamma RIII, and HLA-DRA. This induction was not triggered by adherence, a known activating stimulus, and several lines of evidence showed that induction was not dependent upon interferon gamma (IFN-gamma). Induction was not prevented by neutralizing anti-IFN-gamma antibodies and IFN-gamma was not detected in the SFs using a sensitive enzyme-linked immunosorbent assay. The SFs also were not able to activate the IFN-gamma-activated transcription factor Stat1, thus providing further support for the absence of IFN-gamma. SFs did activate a related signal transducer and activator of transcription (STAT) family factor, termed Stat-SF, which bound specifically to the IFN-gamma response region (GRR), a well-characterized transcription element in the Fc gamma RI promoter. Based upon DNA-binding specificity and mobilities in gel shift assays, and reactivity with specific antisera, Stat-SF likely contains Stat3, or a closely related STAT family member. Neutralization of interleukin 6, a cytokine present in SFs which is known to activate Stat3, abolished the activation of Stat-SF and inhibited the induction of Fc gamma RI expression by SFs. These results demonstrate the activation of monocytes by inflammatory SF and suggest that monocyte activation at an inflammatory site may occur in the absence of IFN-gamma through the triggering of signal transduction pathways that activate STAT transcription factors.

Arthritis, Rheumatoid↗

PubMed2006

[The role of smoking as a risk factor in inflammatory bowel diseases: single center study in Korea].

BACKGROUND/AIMS: Cigarette smoking is the most significant environmental factor identified in inflammatory bowel disease (IBD). Smoking has a beneficial effect on ulcerative colitis (UC) patients. In contrast, Crohn's disease (CD) is associated with smoking, and a detrimental effect of smoking on the course of CD has been demonstrated. The aim of this study was to explore the prevalence in smoking in CD and UC at the time of diagnosis compared with the general population in a single center study. METHODS: Prevalence of smoking at the time of IBD diagnosis were compared between CD and UC patients in Kyung-Hee Medical Center with healthy general population at age-, gender-, and time period-adjusted rates. We investigated the smoking status of IBD patients at the time of diagnosis by telephone interview. There were 178 IBD patients (98 UC patients and 80 CD patients) between January 1995 and December 2004. RESULTS: The male to female ratio in CD and UC were 2:1 and 1:1.4, respectively. The onset of age was 28.2 years and 38.8 years, respectively. The prevalence of smoking was significantly lower in CD and UC patients than in the general population (CD; odds ratio 0.21, 95% confidence interval 0.12-0.41, p<0.001, UC; odds ratio 0.06, 95% confidence interval 0.03-0.14, p<0.001). After statistical adjustment for gender and age at the diagnosis of IBD, the odds ratio of a current smoker diagnosed as UC was 73% lower than that of CD (adjusted odds ratio 0.27, 95% confidence interval 0.12-0.59, p<0.001). In contrast, being a former smoker showed a risk of approximate 1.27-fold higher likelihood of having UC diagnosis (adjusted odds ratio 1.27, confidence interval 0.41-3.95, p=0.68). CONCLUSIONS: Cigarette smoking is protective against developing UC at any age, but is not associated with the development of CD in Korean population. Former smoking is not the high risk factor in developing UC.

Adult↗

PubMed2004

Ameliorating effect of hepatocyte growth factor on inflammatory bowel disease in a murine model.

Hepatocyte growth factor (HGF), a multifunctional cytokine, accelerates intestinal epithelial proliferation. We studied the effects of HGF in mice with trinitrobenzene sulfonic acid-induced colitis, which shows clinical and molecular resemblance to Crohn's disease. Mice with colitis repeatedly were transfected intramuscularly with human HGF cDNA. Weight, survival, histopathology, proinflammatory cytokine mRNAs, and leukocyte infiltration were assessed. Treatment with HGF cDNA induced tyrosine phosphorylation of intestinal c-Met/HGF receptors, inhibited apoptosis, and promoted mitosis in intestinal epithelial cells, accelerating intestinal epithelial restoration and suppressing inflammation. Transfection with HGF cDNA markedly suppressed intestinal mRNA expression of T-helper 1 cytokines such as interleukin-12 and -1beta, interferon-gamma, and tumor necrosis factor-alpha. Numbers of total and CD4-positive T cells, neutrophils, and myloperoxidase activity in intestinal epithelium were diminished by HGF gene transfer, which also prevented weight loss, and improved survival. HGF might prove useful for controlling inflammatory bowel disease.

Animals↗

PubMed1994

[Relationship between hemorheology and pro- and anti-coagulation factors in inflammatory and degenerative vascular diseases].

After having found out an increase in the Von Willebrand Factor (vWF) and a relation between its persistance and seriousness of some vasculities, we looked for a link between changes in vWF level and hemorheology, their role and interdependence in the evolution of the vascular diseases, in complications and in relapses. We studied patients affected with degenerative and inflammatory vascular diseases and we determined rheologic parameters, in traditional and personal innovative way, pro- and anti-coagulation factors, other inflammatory proteins and hematic parameters. As regards coagulation only the vWF appeared increased in a significant way, without differences between two types of vascular diseases. As regards hemorheology, in both of them we measured an increase in the whole blood viscosity but with a different behaviour of its components. In the degenerative vascular diseases there was an increase both in corpuscular viscosity and in the plasma-erythrocyte one, a no significant increase in the plasma viscosity whereas the erythrocyte deformability was in the normal range. In vasculitis there was the highest increase in the plasma and corpuscular viscosities with a decrease in the deformability without changes in the plasma-erythrocyte viscosity. We give some interpretations on their different behaviour and a right meaning of the involved phenomena in every kind of rheologic parameter.

Aged↗

PubMed2003

[The expression of nerve growth factor in inflammatory cells of induced sputum from patients with asthma].

OBJECTIVE: To investigate the expression of nerve growth factor (NGF) in inflammatory cells of induced sputum from patients with asthma. METHODS: Induced sputum samples were collected from 11 asthmatics in exacerbation, 19 asthmatics with stable disease and 11 healthy individuals. Sputum samples of 12 asthmatics with stable disease were collected again after treatment with inhaled corticosteroids (ICS) for 2 weeks. The differential counts of sputum inflammatory cells were studied. NGF was detected using immunocytochemistry and the positive percentages in different cells were measured. Interleukin-5 (IL-5) in sputum supernatants was detected using enzyme-linked immunosorbent assay. RESULTS: NGF was localized in the plasma of macrophages, lymphocytes and granulocytes. 1. In asthmatics with both exacerbation and stable disease, the NGF positive percentages in macrophages [(77.8 +/- 4.8)% and (68.1 +/- 5.3)%], lymphocytes [(43.2 +/- 9.3)% and (34.2 +/- 11.3)%], and granulocytes [(38.7 +/- 6.2)% and (32.1 +/- 3.7)%] were all significantly higher (P < 0.01) than those in the healthy controls [(37.6 +/- 8.4)%, (12.6 +/- 8.5)%, and (12.7 +/- 8.2)%, respectively]. The differences of those indices between patients with exacerbation and patients with stable disease were also significant (P < 0.01). Patients with exacerbation had significantly elevated levels of IL-5 [(124 +/- 71) ng/L] compared with patients with stable disease [(52 +/- 23) ng/L] and the healthy controls [(26 +/- 12) ng/L] (P < 0.01). 2. In the 12 patients with stable disease evaluated after treatment with ICS, the NGF positive percentages in macrophages [(54.3 +/- 7.3)%], lymphocytes [(22.0 +/- 5.6)%], and granulocytes [(27.0 +/- 4.3)%], and the level of IL-5 [(29 +/- 13) ng/L] were all decreased significantly (P < 0.01) compared with the baselines [(67.0 +/- 5.0)%, (36.0 +/- 9.0)%, (32.0 +/- 3.0)%, and (49 +/- 26) ng/L, respectively]. 3. The NGF positive percentages in both macrophages and granulocytes correlated to the sputum lymphocyte counts (r = 0.723, r = 0.630, P < 0.01; respectively) and the levels of IL-5 (r = 0.652, r = 0.636, P < 0.01; respectively). CONCLUSION: The expression of NGF in macrophages and lymphocytes in the airways is upregulated in asthma, which indicates a potential correlation between NGF and airway inflammation in asthma.

Adult↗

PubMed1998

Advances in periodontal diagnosis. 5. Potential inflammatory and immune markers.

The potential inflammatory and immune markers that might detect periodontal disease severity or activity are examined. The role of inflammatory and immune factors passing from the tissues into the gingival crevicular fluid (GCF) are considered. GCF sampling is a necessary part of all diagnostic tests based on gingival and periodontal tissue factors. Inflammatory and immune factors found in GCF are reviewed with special reference to the humoral immune response, complement, cytokines and prostaglandins. The possible development of diagnostic tests based on these factors are discussed.

Antibodies↗

PubMed1997

Genetic risk factors in inflammatory abdominal aortic aneurysms: polymorphic residue 70 in the HLA-DR B1 gene as a key genetic element.

PURPOSE: Evidence of a genetic predisposition to the development of inflammatory abdominal aortic aneurysms (AAAs) exists as a positive family history in 17% of patients. Familial clustering and other similarities between inflammatory AAAs and giant cell arteritis (GCA), which possesses a genetic risk determinant mapped to the HLA-DR molecule, suggest a role of genetic risk factors in inflammatory AAAs. The purpose of this study was to explore whether patients with inflammatory AAAs express disease-relevant genes associated with the HLA-DR region on the short arm of chromosome 6. METHODS: Thirty-seven patients with histomorphologic findings of inflammatory AAA at operation were genotyped for the polymorphism of the HLA-DR B1 and HLA DQ B1 alleles and compared to ethnically matched, healthy control subjects (n = 90). RESULTS: Distribution of HLA-DR B1 alleles was nonrandom in patients with inflammatory AAAs versus control subjects. The HLA-DR B1 alleles B1*15 and B1*0404 were enriched in patients with inflammatory AAAs compared with control subjects (47% versus 27%, and 14% versus 3%; p < 0.05, respectively). Analysis of functionally relevant amino acid polymorphisms encoded by the HLA-DR B1 gene showed relevance at amino acid position 70. HLA-DR B1 alleles overrepresented in patients with inflammatory AAAs express a glutamine substitution at position 70, whereas alleles disfavored in the patient cohort express a negatively charged aspartic acid. Distribution of HLA-DQ B1 alleles were indistinguishable in patients and control subjects. CONCLUSION: These data indicate that a genetic risk determinant can be mapped to the HLA-DR B1 locus in patients with inflammatory AAAs. This association suggests a critical contribution of antigen binding in the pathogenesis of this disease.

Aged↗

PubMed1997

Paradoxical effects of intra-arterial administration of basic fibroblast growth factor on inflammatory angiogenesis in rats.

The authors studied the effects of basic fibroblast growth factor (b-FGF) on inflammatory angiogenesis in rats. In the corneal cauterization model b-FGF was given intra-arterially (i.a.) (carotid) and in the mesenteric window angiogenesis model, topically (i.e., intraperitoneally (i.p.)). The corneal cauterization was done under anaesthesia by topical application of silver nitrate. Mesenteric window angiogenesis was induced by injection of saline or b-FGF for four days. There were the same two groups of treatment in both models b-FGF 2.5 micrograms/kg/day or saline 1.2-5 ml/kg/day. The area of neovessels and the number of polymorphonuclear cells/field were considered for the corneal angiogenesis, the total length of neovessels was measured for the mesenteric window angiogenesis. The results were expressed as mean values (s.d.). When given i.a., b-FGF significantly reduced the number of polymorphonuclear cells three days after corneal cauterization (from 107 +/- 27 to 41.8 +/- 26, p < 0.01) and inhibited the area covered by neovessels (30 +/- 7.7% vs 51 +/- 20%, p < 0.01) after five days. In contrast, given through the extracellular space, it significantly stimulated the length of mesenteric window microvessels (169 +/- 60 mm vs 90 +/- 31 mm, p < 0.05). These results suggest that b-FGF stimulates inflammatory angiogenesis through interaction with extracellular matrix components, but inhibits it directly when given intra-arterially.

Administration, Topical↗

PubMed2006

Immediate inflammatory response and scar formation in wounded vocal folds.

OBJECTIVES: Vocal fold scarring is the major cause of voice disorders after voice surgery or laryngeal trauma. The role of inflammatory factors in vocal fold wound healing and fibrosis has not been adequately investigated. Scarless wound healing has been associated with decreased inflammatory responses. To understand scar formation and develop reliable treatments, it is necessary to control extracellular matrix production and inflammation. Thus, we examined the inflammation profile and extracellular matrix production in wounded vocal folds in the acute phase of wound healing. METHODS: Vocal fold stripping was performed on 30 Sprague-Dawley rats. Vocal fold tissue was collected at 5 time points (4, 8, 16, 24, and 72 hours). We examined the in vivo messenger RNA expression profile of inflammatory factors interleukin 1beta, interferon gamma, tumor necrosis factor alpha, nuclear factor kappa beta, transforming growth factor beta, and cyclooxygenase 2, as well as hyaluronic acid synthases 1 and 2, procollagen subtypes I and III, and elastin synthase in scarred vocal folds after injury, compared to normal vocal folds, using real-time reverse transcription-polymerase chain reaction. RESULTS: The inflammatory factors showed a time-dependent sequence of expression peaks, starting with interleukin 1beta, nuclear factor kappa beta, tumor necrosis factor alpha (4 and 8 hours), and transforming growth factor beta (72 hours). Interferon gamma decreased at 24 hours. Correspondingly, hyaluronic acid synthase 1 expression peaked first (4 and 8 hours), whereas hyaluronic acid synthase 2 expression peaked at 16 hours and again at 72 hours. Procollagen I expression peaked at 72 hours, whereas procollagen III decreased from 8 to 16 hours but peaked at 72 hours. Cyclooxygenase 2 expression was elevated, whereas elastin expression remained constant. CONCLUSIONS: The results show a clear profile of vocal fold inflammation with corresponding changes in extracellular matrix production.

Animals↗

PubMedDate not supplied

Environmental risk factors in inflammatory bowel disease.

Besides a genetic predisposition, a causal role of various environmental factors have been taken into consideration in the etiology of inflammatory bowel disease (IBD). The most consistent association of environmental factors so far identified is the association between non smoking and ulcerative colitis (UC) as well a between smoking and Crohn's disease (CD). Other factors such as oral contraceptives, refined sugar, perinatal events, childhood infections, microbial agents, and domestic hygiene have been found to be associated with ulcerative colitis and Crohn's disease but further evaluation is required to confirm the consistency and to define the strength of the association. Recent data also suggest that measles virus may persist in intestinal tissue and early exposure to the virus may be a risk factor for development of CD. The further investigation of environmental factors on IBD and the explanation of their role is expected to open new avenues for basic scientific research and may lead to the development of a more rational approach to the prevention and treatment of IBD. The available data suggest that UC and CD are heterogeneous disorders of multifactorial etiology in which hereditary and environmental factors interact to produce the disease.

Colitis, Ulcerative↗

PubMed2003

Hepatocyte growth factor ameliorates inflammatory bowel disease in a rat model.

This study was designed to investigate the benefits of administration of hepatocyte growth factor in a rat model of inflammatory bowel disease. Transfection of the HLA-B27 gene into Fisher rats induces a phenotype similar to inflammatory bowel disease. Fisher rats and HLA-B27 rats were divided into six groups: (1) Fisher, intravenous saline; (2) HLA-B27, intravenous saline; (3) HLA-B27, intravenous hepatocyte growth factor; (4) Fisher, luminal saline; (5) HLA-B27, luminal saline; and (6) HLA-B27, luminal hepatocyte growth factor. Rats received a 14-day infusion through an osmotic pump attached to a catheter positioned in either the jugular vein or the terminal ileum. Rats were evaluated for stool character, and gross and microscopic bowel inflammation. Statistics were analyzed using analysis of variance or the Kruskal-Wallis nonparametric test. A value of P<0.05 was significant. Compared to untreated HLA-B27 rats, intravenous administration of hepatocyte growth factor decreased diarrhea by 41% and microscopic inflammation by 54% (P<0.05). Luminal hepatocyte growth factor exposure decreased total bowel lesions by 53% and microscopic inflammation by 40% compared to untreated HLA-B27 rats (P<0.05), but it did not have an effect on diarrhea. Administration of hepatocyte growth factor ameliorates many of the features of bowel disease in this rat model and theoretically could have therapeutic applications in the management of inflammatory bowel disease in humans.

Administration, Topical↗

PubMed2006

[Comparative research of thrombosis animal model induced byendotoxin in combination with carrageenan in different animals].

OBJECTIVE: To compare the development of thrombosis animal model induced by endotoxin(LPS) in combination with carrageenan (Ca) in different animals. METHOD: Two species of rats (SD and Wistar) and three species of mice (Kunming, ICR and Balb/c mice) were employed in the study. The animals of each species were randomly divided into control group and model group (LPS/Ca treatment). The animals in the model group were pretreated with Ca ip at the doses of 25 mg x kg(-1) for rats and 150 mg x kg(-1) for mice, and then treated by LPS iv sixteen hours later, while in the control group were given normal saline (NS). Thrombosis in tails was observed at 24 h after LPS iv. Hematologic parameters were tested for all the animals from each species, and the blood concentration of TNFalpha and IL-6 at different time in SD and Wistar rats were measured. RESULT: LPS/Ca combinatory treatment could induce thrombosis animal model in all five animal species, and the thrombus could be clearly observed on the tails. All species had the similar change in hematologic parameters characterized as the significant decrease of white blood cells and platlets. Inflammatory factors TNFalpha and IL-6 could be largely induced in blood of both SD and Wistar rats at 2 h after LPS iv, but both inflammatory factors only transitorily exist in blood at the early stage of thrombosis model formation. CONCLUSION: LPS/Ca combinatory treatment can successfully induce thrombosis animal model in all tested animal species, and thus this model has extensive animal candidates. The secretion of a large amount of inflammatory factors plays a crucial role in the formation of thrombosis animal model.

Animals↗

PubMed1998

Exposure of T lymphocytes to leflunomide but not to dexamethasone favors the production by monocytic cells of interleukin-1 receptor antagonist and the tissue-inhibitor of metalloproteinases-1 over that of interleukin-1beta and metalloproteinases.

On direct cell-cell contact, stimulated T lymphocytes potently trigger the production of pro-inflammatory factors such as interleukin-1beta (IL-1beta) and matrix metalloproteinases (MMP-1 and MMP-9), as well as anti-inflammatory factors such as IL-1 receptor antagonist (IL-1Ra) and the tissue inhibitor of metalloproteinases (TIMP-1) in peripheral blood monocytes and the monocytic cell line THP-1. Such mechanisms might play an important part in many inflammatory diseases where tissue destruction occurs. To assess whether anti-inflammatory agents such as dexamethasone (DEX) and leflunomide (LF) would affect contact-activation of monocytic cells, T lymphocytes were stimulated by PMA and PHA in the presence or absence of increasing concentrations of drug. LF and DEX (10- 4 M) inhibited the ability of stimulated T lymphocytes to activate monocytic cells by 66-97% and 43-70%, respectively, depending on the readout product. Upon contact with T lymphocytes stimulated in the presence of 10- 5 M LF, the molar ratio of IL-1Ra/IL-1beta and TIMP-1/MMP-1 produced by THP-1 cells was enhanced 3.6- and 1.9-fold, respectively, whereas it was enhanced only 1.3- and 1.4-fold upon contact with T lymphocytes stimulated in the presence of 10- 4 M DEX. Therefore, LF tends to favor the inhibition of pro-inflammatory and matrix-destructive factors over that of anti-inflammatory factors and metalloproteinase inhibitors, thus interfering with both inflammation and tissue destruction. These experiments indicate that LF and DEX have the potential to affect the capacity of stimulated T lymphocytes to activate, on direct cell-cell contact, monocytic cells. Furthermore, flow cytometric analysis revealed that surface molecules of T lymphocytes that were partially involved in contact-signaling of monocytes (i.e., CD69 and CD11) were not modulated by either LF or DEX, suggesting that factors which remain to be identified were mainly involved in the activation of monocytes on direct cell-cell contact.

Anti-Inflammatory Agents, Non-Steroidal↗