Activation of complement in psoriasis.
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Complement Activation↗
Biomedical subjects
J D Bos
Publications and source records attributed to J D Bos.
Enhanced prostaglandin E2 production by monocytes in atopic dermatitis (AD) is not accompanied by enhanced production of IL-6, IL-10 or IL-12.
AD is associated with a bias of the T helper cells to show increased IL-4 and reduced interferon-gamma (IFN-gamma) production. The production of IFN-gamma and IL-4 and the development of Th cells into either high IFN-gamma or high IL-4 producers is strongly influenced by factors produced by antigen-presenting cells (APC), like IL-12 and prostaglandin E2 (PGE2). IL-12 selectively enhances IFN-gamma production and favours the development of IFN-gamma-producing Th cells, whereas PGE2 selectively inhibits IFN-gamma production by Th cells. The aim of this study was to test whether the increased IL-4/IFN-gamma production ratio by Th cells in AD can be explained by an increased PGE2/IL-12 production ratio by the APC. Monocytes were used as APC source. PGE2 and IL-12 production by lipopolysaccharide (LPS)-stimulated monocytes from 12 AD patients and 12 non-atopic controls was determined using two complementary experimental systems, whole blood cultures and purified monocytes. In addition, we determined IL-6 production as a measure of monocyte activation, and IL-10 production because IL-12 production by monocytes is highly influenced by endogenously produced IL-10. The monocytes from AD patients showed normal production levels of IL-6 and IL-10, a two-fold, but non-significant decrease in IL-12 production, and a significantly (three-fold) higher PGE2 production than those from non-atopic controls. Here we show for the first time that enhanced PGE2 production by monocytes in AD is not accompanied by a general rise in cytokine production. We conclude that AD is indeed associated with an increased PGE2/IL-12 production ratio by monocytes.
Adolescent↗
UVB radiation preferentially induces recruitment of memory CD4+ T cells in normal human skin: long-term effect after a single exposure.
Acute, low-doses of ultraviolet (UV)-B radiation affect the immune competent cells of the skin immune system. In this study, we examined the time-dependent changes of the cutaneous T cell population in normal human volunteers following a single local exposure to UV. Solar-simulated UV radiation caused an initial decrease in intraepidermal T cell numbers, even leading to T cell depletion at day 4, whereupon a considerable infiltration of T cells in the epidermis occurred that peaked at day 14. In the dermis the number of T cells was markedly increased at days 2 (peak) and 4 after irradiation, and subsequently declined to the nonirradiated control values at day 10. Double-staining with several T cell markers showed that the T cells, infiltrating the (epi)dermis upon UV exposure, were almost exclusively CD4+ CD45RO+ T cells, expressing an alpha/beta type T cell receptor, but lacking the activation markers HLA-DR, VLA-1, and IL-2R. Application of UVB radiation resulted in similar dynamics of T cells, indicating that the UVB wavelengths within the solar-simulated UV radiation were responsible for the selective influx of CD4+ T cells. In conjunction with UVB-induced alterations in the type and function of antigen-presenting cells (i.e., Langerhans cells and macrophages), the changes of the cutaneous T cell population may also contribute to UVB-induced immunosuppression at skin level in man.
Adolescent↗
Interleukin-17 and interferon-gamma synergize in the enhancement of proinflammatory cytokine production by human keratinocytes.
Keratinocytes are influenced by cytokines released by skin-infiltrating T lymphocytes. IL-17 is produced by activated CD4+ T cells and can stimulate epithelial cells. We investigated whether IL-17 could modulate the cytokine production and cell-surface molecule expression of keratinocytes. The effects of IL-17 were compared with those of IFN-gamma, which is also derived from activated T cells and is a strong stimulator for keratinocytes. IL-17 enhanced the mRNA and protein production of the proinflammatory cytokines IL-6 and IL-8 in a concentration-dependent way, and induced a weak expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR. The production of IL-1alpha and IL-15 was not altered. IFN-gamma augmented the production of IL-6, IL-8, and IL-15 and strongly induced both cell-surface molecules. IL-17 and IFN-gamma showed marked synergism in the stimulation of IL-6 and IL-8 protein secretion and, to a lesser extent, in the induction of ICAM-1 and HLA-DR expression. The majority of the CD4+ and CD8+ T cell clones derived from lesional psoriatic skin expressed IL-17 mRNA, suggesting that skin-infiltrating T cells can produce this cytokine. This IL-17 mRNA expression was detectable in T helper cell type 1 and type 2 and did not correlate with the IFN-gamma or IL-4 production. In addition, IL-17 mRNA is detectable in biopsies from lesional psoriatic skin, but not in nonlesional control biopsies. Our study indicates that IL-17 is a proinflammatory cytokine, which could amplify the development of cutaneous inflammation and may support the maintenance of chronic dermatoses, through stimulation of keratinocytes to augment their secretion of proinflammatory cytokines.
CD4-Positive T-Lymphocytes↗
Effects of UVB on the synthesis of complement proteins by keratinocytes.
UVB exposure of the skin results in increased production of several cytokines by keratinocytes and infiltration of inflammatory cells. We hypothesized that UVB may increase the expression of complement (C) components and C-regulatory proteins by keratinocytes. In vivo, UVB may upregulate these proteins by direct effects or via cytokines released by keratinocytes or infiltrating inflammatory cells. In vitro, UVB may upregulate these proteins only directly, because of dilution of released cytokines in the medium. To test this, we exposed cultured human keratinocytes to UVB (0-64 J per m2) and monitored C3 and Factor B release in the medium by enzyme-linked immunosorbent assay, and surface expression of decay accelerating factor, membrane cofactor protein, and CD59 by flow cytometry. Keratinocytes produced small amounts of C3 and Factor B, which remained unaffected by UVB. UVB (32 J per m2) caused a transient upregulation of all three C-regulatory proteins. Decay accelerating factor expression was maximal at 48 h (1.81 +/- 0.06-fold increase in mean fluorescence intensity over nonexposed cells), membrane cofactor protein at 72 h (2.13 +/- 0.09-fold increase in mean fluorescence intensity), and CD59 at 120 h (1.96 +/- 0.09-fold increase in mean fluorescence intensity), returning to baseline values within 96, 192, and 192 h, respectively. Exposure to 64 J per m2 resulted in significant cell death; cells surviving this dose up to 48 h expressed a higher level of all the three proteins than those surviving 32 J per m2. In conclusion, UVB upregulated membrane cofactor protein, decay accelerating factor, and CD59 on keratinocytes without affecting the constitutive release of C3 and Factor B. Thus, UVB can increase the resistance of keratinocytes against their own C known to be produced excessively in response to cytokines of inflammatory cells that infiltrate the skin following UVB exposure.
Antigens, CD↗
Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds.
In diabetic patients, wound healing is impaired. We studied the pathogenesis behind this clinical observation by characterizing the pattern of deposition of extracellular matrix (ECM) molecules and the cellular infiltrate in chronic (>8 wk) diabetic wounds, compared with chronic venous ulcers and an acute wound healing model. Punch biopsies were obtained from the chronic ulcer margins and control samples were collected from upper leg skin 5, 19, 28 d and 12 and 18 mo postwounding (p.w.). T cells, B cells, plasma cells, granulocytes and macrophages, and the ECM molecules fibronectin (FN), chondroitin sulfate (CS), and tenascin (TN) were visualized using immunohistochemical techniques. Expression of FN, CS, and TN was detected in dermal tissue early in normal wound healing (5-19 d p.w.). Abundant staining was seen 3 mo p.w., returning to prewounding levels after 12-18 mo p.w. In the dermis of chronic diabetic and venous ulcers with a duration of 12 mo or more, a prolonged presence of these ECM molecules was noted. Compared with normal wound healing: (i) the CD4/CD8 ratio in chronic wounds was significantly lower (p < 0.0027) due to a relatively lower number of CD4+ T cells; (ii) a significantly higher number of macrophages was present in the edge of both type of chronic ulcers (p < 0.001 versus day 29 p.w.); and (iii) more B cells and plasma cells were detected in both type of chronic wounds compared with any day in the acute wound healing model (p < 0.04 for CD20+ and p < 0.01 for CD79a+ cells). These data indicate that important differences exist in the cellular infiltrate and ECM expression patterns of acute, healing versus chronic wounds, which may be related to the nonhealing status of chronic wounds.
Acute Disease↗
The millennium criteria for the diagnosis of atopic dermatitis.
Atopic dermatitis forms an active area of basic and clinical research, where important new knowledge about genetics and immunopathogenesis has surfaced over the past years, and where simultaneous development of new and innovative therapies is under way. However, the inclusion of any patient in an atopic dermatitis study, whether it is on its genetics, pathogenesis or therapy, requires a diagnosis which is irrefutable. Since there is no simple and also no complicated laboratory procedure to reach a diagnosis of atopic dermatitis, different sets of clinical criteria have been developed for the purpose of making the diagnosis uniformly in different studies as well as in different study centers. The most commonly used are Hanifin and Rajka's set of diagnostic features, which have major and minor clinical criteria to be fulfilled in order to establish a diagnosis of atopic dermatitis. Recent developments in the immunology of atopy have clearly established the major abnormality in this syndrome, the preferential production of allergen-specific IgE. In this contribution, it is suggested that the presence of such antibodies in a given patient should be a mandatory criterium for the diagnosis of atopic dermatitis. Such a diagnostic test however establishes a diagnosis of atopic syndrome, not atopic dermatitis. Thus, for atopic dermatitis we have to rely, for the time being, on additional clinical criteria. The clinical features described in the literature are critically evaluated, and it is suggested that in addition to the mandatory presence of allergen-specific IgE, 2 of 3 principal criteria (pruritus, typical morphology and distribution, chronic or chronically relapsing) should be present for such a diagnosis. Finally, the minor features originally described by Hanifin and Rajka and later evaluated by others are revised and divided over 4 subcategories; a) related to subclinical eczema; b) related to dry skin; c) extra skin folds; and d) ophthalmological pathology. They are suggested to be used as additional criteria only, needed when clinical suspicion is high but the new mandatory and principal diagnostic criteria described here are inconclusive. For study purposes, we suggest that the mandatory and principal criteria are sufficient. They are now evaluated and validated in ongoing atopic dermatitis treatment studies.
Animals↗
Low-dose narrow-band UVB phototherapy combined with topical therapy is effective in psoriasis and does not inhibit systemic T-cell activation.
BACKGROUND: Psoriasis is a chronic T-cell-mediated inflammatory skin disease which can be treated with topical medication, phototherapy or systemic medication. A subgroup of psoriatic patients does not respond to monotherapy and needs combination therapy. We used low-dose narrow-band UVB phototherapy, combined with balneotherapy, short-contact anthralin, liquor carbonis detergens and calcipotriol for treatment of psoriatic patients in our day care centre. OBJECTIVE: Our purpose was to study the efficacy, induction of erythema and effect on systemic T-cell activation of this combination therapy. METHODS: Skin reflectance spectrophotometry was used to measure skin erythema. The Psoriasis Area and Severity Index (PASI) was used to evaluate psoriatic patients. Serum soluble IL-2 receptor (sIL2-R) levels were measured by an ELISA. RESULTS: The possible erythematogenic effect of low-dose narrow-band UVB irradiation was studied (skin reflectance spectrophotometer) in a control group of psoriatic patients (n = 11). No induction of skin erythema was seen. Subsequently, this low-dose irradiation regimen was used in combination with topical medication in 26 psoriatic patients. A 90% decrease in the PASI was seen after a mean number of 35 treatment sessions. Seventeen patients (65%) remained in remission during the following 6 months. Serum sIL-2R levels were elevated in all patients (mean 913 U/ml) and did not change during treatment. CONCLUSION: Our data indicate that low-dose narrow-band UVB can be used successfully, in combination with topical treatment, in a day care setting to treat psoriatic patients. Since sIL-2R serum levels were not decreased, it can be speculated that this treatment does not induce systemic immunosuppression.
Administration, Topical↗
Molecular heterogeneity of second and fourth components of complement and their genes in systemic sclerosis and association of HLA alleles A1, B8 and DR3 with limited and DR5 with diffuse systemic sclerosis.
Deficiency of the complement component C4 at the functional, protein and gene level and deficiency of complement component C2 at the functional level were investigated and HLA analysis was performed on patients with limited and diffuse systemic sclerosis (SSc). One of the patients with limited SSc (n = 15) had subnormal C4, 1 subnormal C2 and 1 subnormal C4 and C2 activities; the latter patient had HLA alleles A11;B35;Dw1 associated with type II C2 deficiency and therefore most likely had a defect at the C2 locus. One of the patients with diffuse SSC (n = 12) had subnormal C4 and 1 subnormal C4 and C2 activities. C2 deficiencies in patients other than the one with the haplotype associated with C2 deficiency appeared not to be determined by the gene at the C2 locus. The incidence of partial C2 deficiency in a normal Caucasian population is reported to be 16 in 10,000, and that of partial C4 deficiency also appears to be very low. The percentages of C4A*Q0 and C4B*Q0 alleles in normal controls (n = 45) were within the reported range. Seven patients with limited SSc (n = 14) had one or two C4A*Q0 alleles and 2 with diffuse SSc (n = 13) had one C4A*Q0 allele. Thus, the incidence of C4A*Q0 was higher than normal in limited SSc and within the normal range in diffuse SSc. The two-sided Fisher's exact test applied on these data revealed that the association of C4A*Q0 with limited SSc did not reach a significant level (p = 0.10). Two of the 3 patients with limited SSc, who had two C4A*Q0 alleles, carried a heterozygous C4A-21-hydroxylase A (OHA) gene segment deletion as detected by Southern blotting. There was no correlation between the subnormal activity of C4 and the occurrence of one or two C4A*Q0 (and C4A-21-OHA segment deletion). HLA alleles A1, B8 and DR3 (p = 0.002) were associated with limited SSc (n = 23) and DR5(w11) (p = 0.018) with diffuse SSc (n = 17).
Alleles↗
[Immunology in clinical practice. VII. Psoriasis].
A new hypothesis of the pathogenesis of psoriasis holds that psoriasis is an epidermal hyperproliferative disorder resulting from abnormal interaction between T cells and basal layer stem cell keratinocytes. New therapies aimed at reducing T cell activity are most successful, as exemplified by the efficacy of systemic cyclosporine in severe cases of psoriasis. New developments in immunogenetics and immunodermatology are anticipated and it is expected that they will fully explain the chain of pathological events.
Antibodies, Monoclonal↗
A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group.
BACKGROUND: Tacrolimus (FK 506) is an effective immunosuppressant drug for the prevention of rejection after organ transplantation, and preliminary studies suggest that topical application of tacrolimus is effective in the treatment of atopic dermatitis. METHODS: We conducted a randomized, doubleblind, multicenter study that compared 0.03 percent, 0.1 percent, and 0.3 percent tacrolimus ointment with vehicle alone in patients with moderate to severe atopic dermatitis. The ointment was applied twice daily to a defined, symptomatic area of 200 to 1000 cm2 of skin for three weeks. The primary end point was the change in the summary score for erythema, edema, and pruritus between the first and last days of treatment. RESULTS: After three weeks of treatment, the median percentage decrease in the summary score for dermatitis on the trunk and extremities was 66.7 percent for the 54 patients receiving 0.03 percent tacrolimus, 83.3 percent for the 54 patients receiving 0.1 percent tacrolimus, 75.0 percent for the 51 patients receiving 0.3 percent tacrolimus, and 22.5 percent for the 54 patients receiving vehicle alone (P<0.001). The results for the face and neck were similar. The differences among the three tacrolimus groups were not statistically significant. A sensation of burning at the site of application was the only adverse event that was significantly more frequent with tacrolimus than with vehicle alone (P<0.001). Throughout the study, most patients in all three tacrolimus groups had blood concentrations of tacrolimus below 0.25 ng per milliliter. The highest concentration was 4.9 ng per milliliter, which was reported in the group receiving 0.3 percent tacrolimus. CONCLUSIONS: The short-term application of tacrolimus ointment is effective in the treatment of atopic dermatitis, with the sensation of burning being the main side effect.
Administration, Cutaneous↗
Ranitidine does not affect psoriasis: a multicenter, double-blind, placebo-controlled study.
BACKGROUND: Data from open studies suggest that ranitidine has a beneficial effect on psoriasis and is well tolerated. OBJECTIVE: Our purpose was to determine the effectiveness of ranitidine in a 24-week, multicenter, double-blind, placebo-controlled, dose-comparing study of 201 patients with psoriasis. METHODS: Patients with moderate to severe psoriasis who had stopped systemic antipsoriatic therapy, including PUVA and UVB, for at least 10 weeks were included. After a washout period of 2 weeks, patients were randomly allocated to use either ranitidine, 150 mg twice a day; ranitidine, 300 mg twice a day; or placebo for up to 24 weeks. Assessment with the Psoriasis Area and Severity Index was performed at weeks 3, 6, 9, 12, 18, and 24 after randomization. Reduction of the Psoriasis Area and Severity Index score by 70% at the completion of the study was considered a treatment success. RESULTS: The success rates at week 24 in the 300 mg, 600 mg, and placebo groups were 11%, 5%, and 12%, respectively. No significant differences were observed between the three treatment groups at any stage of the study. CONCLUSION: This study provides strong evidence that ranitidine does not affect the skin disease in patients with psoriasis.
Adult↗
In contrast to their murine counterparts, normal human keratinocytes and human epidermoid cell lines A431 and HaCaT fail to express IL-10 mRNA and protein.
In mice, keratinocyte-derived IL-10 is up-regulated by ultraviolet-B (UVB) radiation and plays a major role in UVB-induced immunosuppression. The present study was designed to examine whether a comparable phenomenon can be detected in man. Freshly isolated or cultured normal human keratinocytes (NHK) and keratinocyte cell lines A431 and HaCaT were stimulated with graded doses of UVB (up to 200 J/m2) or with a variety of other stimuli. RNA was extracted at various time points post-stimulation and analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) using four different IL-10-specific primer pairs and RNA from monocytes or T cells as positive controls. We failed to detect IL-10 mRNA in NHK from 40 different donors (breast, abdomen, leg, scalp, foreskin) and in A431 and HaCaT cells, irrespective of the stimulation used and despite successful stimulation. Supernatants of NHK, A431 and HaCaT cultures were negative for IL-10 protein, as tested by four different ELISAs and a bioassay. Murine keratinocytes, stimulated under comparable conditions and tested by the same techniques, displayed a strong expression of IL-10 mRNA and protein. Remarkably, an IL-10 mRNA signal could be detected in NHK after a second round of PCR amplification. Because NHK suspensions are contaminated with Langerhans cells, melanocytes and possibly fibroblasts, we tested pure populations of each individual cell type to determine the origin of this IL-10 mRNA. Our results clearly indicate that NHK, Langerhans cells and fibroblasts fail to express IL-10 and that melanocytes are the principal source of IL-10 mRNA in normal human epidermis.
Animals↗
Despite the presence of UVB-induced DNA damage, HLA-DR+ cells from ex vivo UVB-exposed human skin are able to migrate and show no impaired allostimulatory capacity.
In this study, we investigated the effect of ultraviolet B radiation on human Langerhans cell function. Normal human skin was irradiated ex vivo with single doses of ultraviolet B. For assessment of T-cell stimulatory function, cells that spontaneously migrated from epidermal sheets were used, whereas full-thickness skin biopsies were used to investigate alterations in migratory properties. The cells migrating from ultraviolet B-exposed epidermal sheets demonstrated a decrease in the percentage of HLA-DR positive Langerhans cells, as well as a reduced capacity to induce proliferation of allogeneic T cells, when compared with cells migrating from nonexposed sheets. When a correction was made for the decreased number of HLA-DR positive Langerhans cells migrating from ultraviolet B-exposed epidermis, however, it appeared that the capacity to induce T-cell proliferation was identical for Langerhans cells migrating from ultraviolet B-exposed and nonexposed epidermis. The presence of ultraviolet B-induced DNA damage could be demonstrated in the Langerhans cells from ultraviolet B-treated skin, indicating that the cells had received significant doses of ultraviolet B. As regards the effect of ultraviolet B on migratory properties of Langerhans cells, we found not only that reduced numbers of CD1a-positive Langerhans cells migrated from the ultraviolet B-exposed full-thickness skin, but also that there was a reduction in CD1a-positive Langerhans cells in the epidermis. This implies that ultraviolet B induces death of Langerhans cells as well as loss of cell surface molecules rather than altering Langerhans cells migration, whereas the Langerhans cells that were still able to migrate fully retained the capacity to activate allogeneic T cells.
Antigen-Presenting Cells↗
Extracorporeal photochemotherapy (photopheresis) induces apoptosis in lymphocytes: a possible mechanism of action of PUVA therapy.
The mechanism of action of psoralen plus UVA (PUVA) and photopheresis is not entirely understood. These therapies are assumed to be immunomodulating partly by gradually decreasing leukocyte viability. We investigated whether this delayed form of cell death was due to apoptosis. Untreated and treated (PUVA exposed) leukocytes obtained from six patients with systemic sclerosis and (untreated) leukocytes from healthy control individuals were studied. Qualitative gel electrophoresis and quantitative in situ nick translation analysis of DNA fragmentation was performed. Apoptosis of the treated cells did occur (gel electrophoresis) after 24 h. At t = 0 h, immediately after exposure to PUVA, there was no evidence of DNA fragmentation in the treated cells. The percentage of treated cells undergoing apoptosis was 20-55% at t = 24 h (in situ nick translation). The untreated leukocytes of the patients and the healthy individuals showed no distinctive rise in apoptotic cells. Apoptosis of the leukocytes after PUVA or photopheresis treatment might be a mechanism of action and might explain the therapeutic response.
Apoptosis↗
Prolonged increase of cis-urocanic acid levels in human skin and urine after single total-body ultraviolet exposures.
Cis-urocanic acid (cis-UCA), a mediator of immunosuppression, is formed from trans-UCA upon UV-exposure of the skin. This study describes a liquid chromatographic method for the simultaneous quantification of cis- and trans-UCA in skin, urine and plasma of nonirradiated volunteers. It also describes cis- and trans-UCA kinetics in UV-irradiated volunteers. New procedures to remove interfering substances from urine and plasma are reported. Normal levels of cis-UCA in skin, urine and plasma of nonirradiated volunteers were 0.5 nmol/cm2, 0.03 mumol/mmol creatinine (median 0.00) and undetectable and those of trans-UCA were 17.1 nmol/cm2, 1.36 mumol/ mmol creatinine and 0.5 microM, respectively. Upon single total body UVB (290-320 nm) exposures of 250 J/m2, epidermal cis-UCA levels immediately reached a maximum and returned to basic levels 3 weeks later. The cis-UCA levels in urine reached a maximum in 5-12 h postirradiation and reached baseline values in 8-12 days. Additionally, a single total body UVA (320-400 nm) irradiation of 200 kJ/m2 yielded a similar pattern. The kinetics of cis-UCA in plasma could not be followed due to low concentrations; however, that of skin and urine was informative in relation to solar exposures and phototherapy.
Adolescent↗
The skin as an organ of immunity.
During evolution, the skin has developed a specific immunological environment that is known as the skin immune system (SIS). A substantial number of immunological phenomena exemplify the special place the skin occupies as a peripheral immune organ. These include the continuous exposure to sun rays, with subsequent immunological consequences, an area of investigation known as photoimmunology. Also special is the presence of a dense network of dendritic antigen-presenting cells (Langerhans cells) in the epidermis, which are functionally related to the skin-specific phenomenon of the contact allergy type of delayed hypersensitivity. The acronym SIS is designed to give a complete picture of the skin's functions as an immunological organ, and includes the humoral systems in addition to the cellular subsets taking part in it. In this article, the history of the development of immunological concepts of skin is exemplified with some recently explored areas of immunodermatological research.
Animals↗
Effect of calcitriol on the production of T-cell-derived cytokines in psoriasis.
Although the use of vitamin D analogues in the treatment of psoriasis has been an important new development, the mechanisms of action of these drugs are not fully understood. Psoriasis results from hyperproliferation of keratinocytes, and various studies attribute a crucial role to the locally infiltrating T lymphocytes. In an attempt to add to the understanding of the mechanisms of calcitriol therapy, we determined the effect of this drug on T cells by studying its effect on proliferation and on the production of various cytokines by T-cell clones prepared from psoriatic skin after non-specific activation with the combination of phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA). The addition of increasing doses (10(-9)-10(-5) mol/l) of calcitriol to these T cells resulted in a dose-dependent inhibition in lymphocyte proliferation and in production of the type 1 cytokines IFN-gamma and IL-2, the type 2 cytokines IL-4 and IL-5. The general cytokines TNF-alpha and GM-CSF were not significantly inhibited. These data suggest that calcitriol is involved in the treatment of psoriasis via inhibition of the expansion, and cytokine production, of skin-infiltrating T lymphocytes.
Calcitriol↗