PubMed Health⌕ Search

Biomedical subjects

E Schmitt

Publications and source records attributed to E Schmitt.

At least 19 recordsLinked to original sources
PubMed1995

Opposing effects of TGF-beta 2 on the Th1 cell development of naive CD4+ T cells isolated from different mouse strains.

The development of naive dense CD4+ T cells from different mouse strains toward Th1 cells, as monitored by measuring secondary IFN-gamma production, was affected by TGF-beta 2 in a differential way. Th1 cell development of naive CD4+ T cells from strains C57Bl/6, BALB/c, and NMRI primed by immobilized anti-CD3 mAb was strongly inhibited in the presence of TGF-beta 2. Even when the Th1 cell-inducer IL-12 was added, the same effect of TGF-beta 2 was observed. In contrast, Th1 development was substantially promoted by TGF-beta 2 with T cells from C3H/He and CBA/J mice. Further analyses using CD4+ T cells from (C57Bl/6xCBA/J)F1 hybrids or DBA/1 mice showed that Th1 development was inhibited by TGF-beta 2 if the T cells were activated by anti-CD3 mAb, but it was enhanced upon costimulation with anti-CD28 mAb. Determination of primary IL-2 production revealed that T cells from (C57Bl/6xCBA/J)F1 and DBA/1 mice produced low amounts of IL-2 following stimulation by anti-CD3 mAb alone and comparatively high amounts after coactivation by anti-CD28 mAb. In the presence of TGF-beta 2, the production of IL-2 was completely suppressed if such T cells were activated solely by anti-CD3 mAb, but it was only partially inhibited after costimulation by anti-CD28 mAb. Furthermore, TGF-beta 2-promoted Th1 development of such T cells was strongly inhibited after neutralization of endogenously produced IL-2 and completely restored by the addition of human IL-2. Thus, our results indicate that the TGF-beta 2-mediated stimulation of Th1 cell development requires the presence of relatively high concentrations of IL-2. Therefore, the opposing effect of TGF-beta 2 on the Th1 cell development of naive CD4+ T cells from different mouse strains appears to be the result of the variable potency of the respective CD4+ T cells to produce IL-2 in the presence of TGF-beta 2.

Animals↗
PubMed1995

Administration of interleukin 12 in combination with type II collagen induces severe arthritis in DBA/1 mice.

The induction of arthritis in DBA/1 mice usually requires immunization with the antigen type II collagen emulsified with Mycobacterium tuberculosis in oil. Here we describe that interleukin 12 (IL-12) can replace mycobacteria and cause severe arthritis of DBA/1 mice when administered in combination with type II collagen. Immunization of DBA/1 mice with type II collagen emulsified in oil alone resulted in a weak immune response, and only a few animals (10-30%) developed arthritis. Administration of IL-12 for 5 days simultaneously with each immunization strongly enhanced the anti-type II collagen immune response. Collagen-specific interferon gamma (IFN-gamma) synthesis by ex vivo activated spleen cells was enhanced 3- to 10-fold. IFN-gamma was almost completely produced by CD4+ T cells. Furthermore, the production of collagen-specific IgG2a and IgG2b antibodies was upregulated 10- to 100-fold. As a consequence, the incidence of arthritis in the group of mice immunized with collagen plus IL-12 was very high (80-100%). The developing arthritis was severe, involving approximately 50% of all limbs with strongly increased footpad thickness in most cases. Furthermore, histological examination revealed massive, mainly polymorphonuclear cell infiltration, synovial hyperplasia, cartilage and bone destruction, as well as new bone formation. In many cases, this resulted in the complete loss of joint structure. Neutralization of IFN-gamma in vivo prevented the development of arthritis in collagen-immunized and IL-12-treated mice. In conclusion, our data show that in vivo administered IL-12 can profoundly upregulate a T helper I-type autoimmune response, resulting in severe joint disease in DBA/1 mice.

Animals↗
PubMed1995

Chromosomal analysis in young vs. senescent human fibroblasts by fluorescence in situ hybridization: a selection hypothesis.

Almost all previous studies on chromosomal analysis related to in vitro aging of human fibroblasts were done using only metaphase chromosomes. However, this procedure may provide only partial information since the aneuploidy presumably hidden in interphase cells would remain undetected. For this reason, we have analyzed aneuploidy both at interphase and at metaphase. Female (IMR-90) and male (IMR-91) cells were grown from the lowest to the highest population doubling levels and aneuploidy analysis was done by FISH with alpha-satellite DNA probes of 15 autosomes and two sex chromosomes. Our data on total aneuploidy in young cells indicate that significantly higher proportions of cells with aneuploidy can be detected at interphase than at metaphase. This presumably indicates that during active division of young cells, more aneuploid than diploid cells are selected against entry to mitosis. In contrast, interphase senescent cells from both strains show significantly fewer aneuploid nuclei than do young cells at interphase. This probably indicates that during senescence, there is greater selective pressure in the culture against long-term survival of aneuploid cells than against survival of diploid cells. Our study shows that cellular dynamics with respect to aneuploidy involving various chromosomes differs significantly at interphase and at mitosis during in vitro aging of human fibroblasts, and we propose a 'Selection Hypothesis' as an explanation to our findings.

Aneuploidy↗
PubMed1995

Viable rat Kupffer cells synthesize but do not secrete interleukin-1: indications for necrosis-induced maturation of interleukin-1 alpha, but not of interleukin-1 beta.

Interleukin-1 is involved in host defense to infection and injury. In this work synthesis and secretion of IL-1 by cultured rat liver macrophages (Kupffer cells) in response to lipopolysaccharide were investigated. IL-1 was found only intracellularly as 31-kD (pro-IL-1 alpha) and 34-kD (pro-IL-1 beta) proteins. No mature 17-kD IL-1 alpha or IL-1 beta was detected in cell lysates or supernatants. Pulse-chase experiments showed that there was no release of IL-1 even after 24h, although pro-IL-1 continuously disappeared from the cells. Cultures were lysed by freezing-thawing. Pro-IL-1 beta was then found in the supernatants, but pro-IL-1 alpha was processed into several smaller fragments. A 17-kD protein could represent the mature IL-1 alpha. The results indicate that Kupffer cells are not able to secrete biologically active mature IL-1 proteins. By lysis of the cells. IL-1 is released. Pro-IL-1 alpha is processed, but pro-IL-1 beta seems to need further activation processes.

Animals↗
PubMed1995

IL-4 renders mast cells functionally responsive to endothelin-1.

It has previously been shown that mouse bone marrow-derived mast cells (BMMC) synthesize and secrete endothelin-1 (ET-1) and express ETA-type endothelin receptors (ETA-R). The study presented here was designed to elucidate the influence of different cytokine conditions for cellular differentiation and maturation on the ability of primary mouse BMMC to respond to exogenous ET-1. BMMC were grown for 2 wk in IL-3 alone and then cultured for 2 to 3 wk with kit ligand (KL) and/or IL-3 in the presence or absence of IL-4. ET-1 induced a very rapid (< or = 1 min) and dose-dependent release of histamine and serotonin from BMMC cultured in the presence of both IL-3 and IL-4. The effect of ET-1 was quantitatively comparable with IgE/Ag-induced mediator release and comprised up to 20% and 16% of total cellular histamine and serotonin, respectively. In BMMC grown with KL or KL plus IL-3, a substantial effect of ET-1 on amine release was only observed when IL-4 had been included in the culture medium. These IL-4 effects could not be observed if BMMC grown in IL-3 and/or KL were preincubated for 1 or 24 h with IL-4 before activation with ET-1, suggesting that a differentiation process rather than a functional priming effect had been initiated by IL-4. In BMMC, the histamine and serotonin release induced by ET-1 (10(-6) M) was inhibited by an ETA-R-specific antagonist (cyclic [D-Asp-Pro-D-Val-Leu-D-Trp]) in a dose-dependent manner, with complete inhibition at an antagonist concentration of 10(-8) M. ET-1 stimulated leukotriene C4 biosynthesis up to 4.5-fold in BMMC cultured in the presence of IL-4. No such ET-1 effect was observed in BMMC cultured in media containing IL-3, KL, or a combination of both cytokines. Peritoneal cells (containing 2 to 3% serosal mast cells) obtained from BALB/c mice released 87 +/- 2% of histamine within 1 min after challenge with ET-1. Our results demonstrate that ET-1 can directly act as a histamine and serotonin secretagogue and as a stimulator of leukotriene C4 production in mast cells. IL-4 appears to be critically involved in the differentiation of immature mast cell precursors to an ET-1-reactive phenotype.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1995

Interleukin-12 profoundly up-regulates the synthesis of antigen-specific complement-fixing IgG2a, IgG2b and IgG3 antibody subclasses in vivo.

The influence of the cytokine interleukin-12 (IL-12) on humoral immune responses was studied in vivo. CBA/J mice immunized with protein antigens (keyhole limpet hemocyanin, phospholipase A2) adsorbed to aluminum hydroxide (Alum) develop a Th2-like immune response characterized by the production of large amounts of IgG1 as well as some IgE but little IgG2a, IgG2b and IgG3 antibodies. IL-12 is a cytokine that promotes the development and the activation of Th1 cells. Th1 cells are involved in the induction of cellular immunity, which is characterized by low or absent antibody production. On the other hand, some Th1-like immune responses are associated with a strong antibody production of the IgG2a, IgG2b and IgG3 subclasses. Thus, we investigated whether treatment with IL-12 would down-regulate the humoral immune response or stimulate antibody production of the IgG2a, IgG2b and IgG3 subclasses. We observed that: 1) administration of IL-12 to mice together with protein antigens adsorbed to Alum strongly enhanced the humoral immune response by increasing the synthesis of antigen-specific antibodies of the IgG2a, IgG2b and IgG3 subclasses 10- to 1000-fold. The synthesis of IgG1 was not or only slightly (2-5-fold) enhanced, whereas that of the IgE isotype was suppressed. 2) These effects of IL-12 were observed when high (10 micrograms, 100 micrograms) or low doses (0.1 microgram) of antigen were used for immunization. 3) Titration of IL-12 in vitro revealed that IgG2a is strongly up-regulated over a wide dose range of IL-12 (10 to 1000 ng/day). 4) The effects of IL-12 in vivo are at least partially interferon (IFN)-gamma-dependent because an anti-IFN-gamma mAb in combination with IL-12 prevented most of the enhanced IgG2a production. 5) Mice receiving IL-12 showed a strong up-regulation of IFN-gamma but no inhibition of IL-5 synthesis by spleen cells activated ex vivo with antigen. These results suggest that IL-12 is a potent adjuvant for enhancing humoral immunity to protein antigens adsorbed to Alum, primarily by inducing the synthesis of the complement-fixing IgG subclasses 2a, 2b and 3.

Aluminum Hydroxide↗
PubMed1995

Co-activation of naive CD4+ T cells and bone marrow-derived mast cells results in the development of Th2 cells.

Activation of naive dense CD4+ T cells by plate-bound anti-CD3 antibodies favors the development of Th1 cells which, upon re-stimulation, produce significant amounts of IFN-gamma but no IL-4. However, co-activation of such naive T cells in the presence of IgE [anti-dinitrophenyl (DNP)]-loaded bone marrow-derived mast cells (BMMC) on plates coated with anti-CD3 antibodies and DNP-BSA led to the development of IL-4-producing Th2 cells. The same result could be observed if irradiated (800 rad) BMMC were applied as co-stimulators. Moreover, BMMC could be replaced by the supernatant of IgE-activated BMMC suggesting that a soluble mediator, presumably IL-4, was responsible for this effect. This assumption was substantiated using neutralizing anti-IL-4 antibodies which abolished the BMMC-mediated Th2 development in all cases. Addition of IL-12, a cytokine that was shown to antagonize the Th2-promoting effect of IL-4 in vivo, could not inhibit the development of IL-4-producing T cells, but gave rise to a T cell population which produced relatively high amounts of IL-4 and IFN-gamma. Since BMMC represent the in vitro equivalent of mucosal mast cells these data suggest that IgE-activated mucosal mast cells can bias an emerging T cell dependent immune response towards a Th2 dominated reaction by the initial production of IL-4.

Animals↗
PubMed1995

[Analysis of complications of thyroid surgery: recurrent paralysis et hypoparathyroidism. On a series of 588 cases].

The purpose of this report is to study the incidence of two main complications in thyroid surgery without systematic search for recurrent laryngeal nerve, by intracapsular thyroidectomy: temporary and chronic laryngeal recurrent paralysis (after six months), temporary hypoparathyroidism and chronic hypoparathyroidism (unrecovering normal function after six months). We have retrospectively analysed 588 patients from 1981 to 1994. There were 247 total or subtotal thyroidectomies and 341 loboisthmectomies (isolated thyroid nodules). We obtained over this 588 cases 0.3% of chronic laryngeal paralysis and 1.4% of chronic hypoparathyroidism. If the cost of surgery for thyroid nodules is low (0.3% of chronic recurrent paralysis and 0% of chronic hypoparathyroidism), it is more important for total or subtotal thyroidectomies (respectively 1.2% and 3.2%). We conclude that in thyroid surgery, there is no higher risk for the recurrent nerve without dissection of this one, but we note that, without obvious explanation, rates of permanent hypoparathyroidism are not better than in others publications.

Humans↗
PubMed1994

IL-9 production of naive CD4+ T cells depends on IL-2, is synergistically enhanced by a combination of TGF-beta and IL-4, and is inhibited by IFN-gamma.

Dense CD4+ T cells isolated from naive mice produce only trace amounts of IL-9 when stimulated by immobilized anti-CD3 in combination with anti-CD28 Abs. In this situation, IL-9 production is significantly stimulated by TGF-beta and further enhanced by the addition of IL-4, which, by itself, has only a minimal influence. IFN-gamma was found to inhibit the enhancing effect of IL-4. However, increasing amounts of IL-4 in the presence of a constant concentration of IFN-gamma could overcome the inhibitory activity of IFN-gamma. The application of CD4+ T cells isolated from IL-2 knockout mice unequivocally revealed that IL-2 is essential for the production of IL-9 by T cells. In addition, the use of T cells from IL-4 knockout mice elucidated that the basic (IL-2 + TGF-beta) mediated IL-9 production is independent of IL-4. Therefore, our results demonstrate that optimal IL-9 production of naive dense CD4+ T cells is positively regulated at different levels: 1) by IL-2, which is essential for IL-9 secretion; 2) followed by TGF-beta, which promotes a considerable increase in IL-9 production above the level induced by IL-2; and 3) finally, by IL-4, which requires the presence of IL-2 and TGF-beta to strongly enhance the production of IL-9. IFN-gamma inhibits the production of IL-9 mainly at the level of IL-4 by neutralizing the effect of this cytokine.

Animals↗
PubMed1994

Methionyl-tRNA synthetase needs an intact and mobile 332KMSKS336 motif in catalysis of methionyl adenylate formation.

The family of aminoacyl-tRNA synthetases may be split into two classes according to the occurrence of specific combinations of peptide motifs. This study deals with the functional role of the KMSKS motif, which, in association with the HIGH motif, defines class 1 aminoacyl-tRNA synthetases. Each residue in the 332KMSKS336 sequence of Escherichia coli methionyl-tRNA synthetase, as well as R337 and the two surrounding G330 and G338 residues, were mutagenized. The comparison of the kinetic and equilibrium parameters of the methionine activation reaction sustained by the resulting variants enables the following conclusions to be drawn. (1) Mutation of all the residues studied strongly destabilizes the transition state for the formation of methionyl adenylate whilst changing moderately the stability of the ground state ternary complex enzyme, methionine: ATP-Mg2+. The consequences of the mutations are also reflected at the level of the stability of the ground state enzyme, methionyl adenylate:PPi-Mg2+ complex which is systematically decreased. (2) The substitution with alanine of any one of the three basic residues K332, K335 and R337 destabilizes the transition state by more than 3.2 kcal/mol, while substitution of the non-basic residues M333, S334 or S336 destabilizes it by at most 2.5 kcal/mol. Such a difference may reflect different modes of action of the residues, with the basic ones directly interacting with the beta and gamma phosphates of the ATP-Mg2+ substrate and the non-basic ones playing a structural role and/or participating in mobility of the enzyme region carrying the motif. (3) Modification of G330 or G338 to a proline markedly decreases the kinetic rate of methionyl adenylate formation. This behaviour suggests that the flexibility of the KMSKS loop in the structure of methionyl-tRNA synthetase is required to reach the transition state during formation of methionyl adenylate.

Adenosine↗
PubMed1994

A sensitive and specific bioassay for the detection of human interleukin-10.

Interleukin-10 (IL-10) is a novel cytokine that is produced by T cells, macrophages, B cells and keratinocytes. It has been shown to inhibit cytokine production and proliferation by T cells when macrophages are used as accessory or antigen presenting cells. Monokine production by macrophages is effectively downregulated by IL-10 and it can be used as a growth factor by CD4, CD8 and gamma/delta positive T cells as well as mast cells and B cells. It is because of these pleiotropic immunoregulatory effects that the detection of IL-10 in the supernatants of T cells, B cells, macrophages and other cells is important for many scientific questions. Here we describe a simple and sensitive bioassay specific for human IL-10 using the IL-10 dependent growth of the mouse mast cell line D36. Our data show that this assay is not crossreactive with hIL-1 beta, hIL-2, hIL-3, hIL-4, hIL-5, hIL-6, hIL-9, hIL-12, hGM-CSF and hTNF-alpha and that it can be completely blocked by an antibody against human IL-10. The hIL-10 induced growth of the D36 cell line is dependent on the presence of mIL-4. Human IL-10 can be measured in a concentration range from approximately 10 U/ml to 0.05 U/ml. This assay is only of limited use for the measurement of IL-10 in human blood samples since it is inhibited by the presence of human serum.

Biological Assay↗
PubMed1994

Differential effects of interleukin-12 on the development of naive mouse CD4+ T cells.

The influence of interleukin (IL)-12 and IL-4 on the differentiation of naive CD4+ T cells was studied in an accessory cell-free in vitro system. Dense CD4+ T cells were purified from unimmunized mice and activated using immobilized anti-CD3 monoclonal antibodies (mAb) in the presence of IL-4, IL-12, or a combination of both cytokines, and restimulated after 6 days by re-exposure to anti-CD3-coated culture wells. T cells initially activated in the presence of IL-4 produced substantial amounts of IL-4 and trace amounts of interferon (IFN)-gamma after restimulation at day 6 with plate-bound anti-CD3 mAb. By contrast, T cells primed in the presence of IL-12 produced high levels of IFN-gamma and only minimal amounts of IL-4, thus indicating that IL-12 and IL-4 by acting directly on stimulated naive CD4+ T cells support the development of TH1 and TH2 cells, respectively. When naive CD4+ T cells were stimulated in the presence of IL-12 together with IL-4 in comparable concentrations, the effect of IL-12 on TH1 differentiation was largely inhibited by IL-4. On the other hand, IL-12 exerted no inhibitory effect on IL-4-induced TH2 differentiation but rather enhanced the production of IL-4 after restimulation of the respective T cells. Decreasing amounts of IL-4 in combination with a high level of IL-12 led to an increasing production of IFN-gamma by the emerging T cells and, simultaneously, to a relatively high production of IL-4. These data were confirmed by time-course experiments which revealed that the delayed addition of IL-4 to IL-12-primed T cell cultures resulted in a gradual restoration of IFN-gamma production whereas in parallel the secretion of IL-4 was not reduced over a wide period of delay (6-72 h). These results, therefore, demonstrate that (a) IL-4 dominates the effect of IL-12, (b) IL-12 promotes the development of TH1 cells; however, in the presence of IL-12 and relatively high levels of IL-4 also the development of TH2-like cells is slightly but significantly enhanced by IL-12, and (c) high amounts of IL-12 in combination with relatively low levels of IL-4 give rise to a T cell population that upon rechallenge exhibited a cytokine profile resembling that of TH0 cells.

Animals↗
PubMed1994

T helper type 1 development of naive CD4+ T cells requires the coordinate action of interleukin-12 and interferon-gamma and is inhibited by transforming growth factor-beta.

It was observed in vitro and in vivo that both interferon (IFN)-gamma and interleukin (IL)-12 can promote the development of T helper type 1 (TH1) cells. Since IL-12 was shown to be a costimulator for the production of IFN-gamma by T or natural killer (NK) cells, IL-12 might play only an indirect role in TH1 differentiation by providing IFN-gamma which represents the essential differentiation factor. Using anti-CD3 monoclonal antibody (mAb) for activation of naive CD4+ T cells in the absence of accessory cells we could demonstrate that costimulation by IFN-gamma alone results only in marginal TH1 development. Similarly, IL-12 in the absence of IFN-gamma is only a poor costimulator for inducing differentiation towards the TH1 phenotype. Our data indicate that both cytokines are required to allow optimal TH1 development and that IL-12 has a dual role, it promotes differentiation by direct costimulation of the T cells and also enhances the production of IFN-gamma which serves as a second costimulator by an autocrine mechanism. Another cytokine that was reported to favor TH1 differentiation in certain experimental systems is transforming growth factor (TGF)-beta. With naive CD4+ T cells employed in this study TGF-beta strongly inhibited the production of IFN-gamma triggered by IL-12 as well as the IL-12-induced TH1 development. When TGF-beta was combined with anti-IFN-gamma mAb for neutralization of endogenous IFN-gamma the TH1-inducing capacity of IL-12 was completely suppressed.

Animals↗
PubMed1994

Effects of human recombinant interleukins on stimulation-evoked noradrenaline overflow from the rat perfused spleen.

Experiments were carried out in the isolated spleen of the rat to study in a lymphoid organ the influence of interleukins (ILs) on noradrenaline release. Spleens were perfused with Tyrode's solution and the overflow of endogenous noradrenaline was determined by HPLC with electrochemical detection. Perivascular electrical stimulation (4 or 10 Hz, 20-28 mA, 2 min) caused an increase in noradrenaline overflow and in perfusion pressure, both of which were markedly reduced by perfusion with Ca(2+)-free solution, abolished by tetrodotoxin, unaffected by hexamethonium, and subject to alpha 2-adrenoceptor- and muscarinic receptor-mediated modulation as shown by the effects of rauwolscine and methacholine. Human recombinant IL-1 beta and IL-2 and mouse recombinant IL-2 10 ng/ml failed to affect the evoked overflow of noradrenaline after an exposure time of 15 min. In contrast, human recombinant IL-1 beta and IL-2 0.1 ng/ml reduced the evoked overflow after exposure for 80 min; the inhibition tended to increase 30 min later despite washout. Murine recombinant IL-2 1.2 ng/ml caused no change after contact with the tissue for 80 min but there was an inhibition 30 min later after washout. Human recombinant IL-6 (0.1 ng/ml) caused no significant change. The inhibitory effect of low concentrations of IL-1 beta and IL-2 supports the idea that locally produced mediators of the immune system may affect neuronal function.

Animals↗
PubMed1994

Expression of interleukin 10 in human melanoma.

The expression of interleukin 10 (IL-10) mRNA in human malignant melanoma was investigated by reverse transcriptase polymerase chain reaction analysis. Selective expression of IL-10 mRNA in tissues of primary melanomas and melanoma metastases was found in comparison with normal skin. In addition, strong expression of IL-10 mRNA and of biologically active IL-10 was detected in 3 out of 13 melanoma cell lines. Normal melanocytes consistently expressed low levels of IL-10 mRNA but did not produce detectable IL-10 protein, nor did keratinocytes or fibroblasts. The production of biologically active IL-10 by melanoma cell lines suggests that IL-10 mRNA in melanoma lesions may derive at least in part from the tumour cells themselves. Tumour-infiltrating cells, however, could also be a source of IL-10 in melanoma tissues. The presence of IL-10 in melanoma lesions may contribute to the postulated 'paralysis' of an anti-melanoma immune response.

Gene Expression↗
PubMed1994

Topical calcipotriol for psoriasis--an immunohistologic study.

The aim of the present study was to investigate the distribution of Langerhans cells and T cells in the lesions and also the phenotypic expression of markers of activation on lesional T cells and keratinocytes, before and after 2 weeks of topical treatment of 7 psoriatic patients with calcipotriol. Before treatment, the infiltrate was composed mainly of T cells and there was decreased expression of CD1 on the intra-epidermal Langerhans cells. ICAM-1 and EGF receptor were present throughout the epidermis, but keratinocytes expressing Transferrin receptor were detected only in the basal layer. After 14 days of calcipotriol therapy, there were significantly fewer CD4T cells in the dermis and an increased number of intraepidermal CD1 + Langerhans cells. ICAM-1 expression on lesional keratinocytes was reduced in all patients, but the expression of EGF receptor was decreased in 3 patients only, and Transferrin receptor expression on keratinocytes had not changed. All these changes were concurrent with moderate clinical improvement of the lesions. The results suggest that in the early stages of the clinical response to calcipotriol there is an immunomodulating effect of the drug associated with variable decreases in keratinocyte expression of markers of activation.

Administration, Topical↗
PubMed1994

Topical calcipotriol (MC 903) for psoriasis: a clinical study.

Calcipotriol, a non-calcemic vitamin D3 analogue, inhibits the proliferation and is necessary for final differentiation of keratinocytes. The aim of the present study was to determine the efficacy and tolerability of calcipotriol ointment in patients treated for 6 weeks. Twenty patients with chronic plaque-type psoriasis were treated twice daily with calcipotriol ointment 50 ng/g. After 6 weeks' treatment there was a marked and statistically significant decrease in the PASI score values for 17 patients, no improvement was seen in 1 patient and local adverse events occurred in 2. Hypercalcemia or other laboratory abnormalities did not develop in any patient.

Administration, Topical↗