Dexamethasone is a widely used anti-inflammatory agent for a broad spectrum of diseases. The effectiveness of this agent is thought to be due to the capacity to modulate cytokine production in inflammatory cells. We examined the effects of dexamethasone on expressions of interferon gamma (IFN-gamma) and interleukin 4 (IL-4) by human peripheral blood mononuclear cells (PBMCs) in response to interleukin 12 (IL-12). Dexamethasone (10-5 M) inhibited IFN-gamma secretion, through direct suppression of IFN-gamma, IL-12 receptor (IL-12R) -beta1, and -beta2 expressions. Conversely dexamethasone increased IL-4 secretion as well as IL-4 expressions by PBMCs in response to IL-12. In addition, dexamethasone increased expression of suppressor of cytokine signalling (SOCS)-1, which inhibits JAK-STAT pathway of IL-12R signalling. The result of our study suggested that dexamethasone directly inhibited IFN-gamma expression, through suppression of IL-12 signalling and indirectly increases IL-4 expression, through suppression of IFN-gamma expression.
Dexamethasone* ; Humans ; Interferons ; Interleukin-12* ; Interleukin-4* ; Receptors, Interleukin-12

No Abstract Available.
Humans ; Interleukin-12* ; Interleukin-18* ; Tuberculosis, Pleural*

The cytolytic activity of CD4' T cells, both human and murine, has been clearly demonstrated in the immune response to mycobacterial infection and suggested to play a significant role in the protection and immunopathology. However, Uttle is known about the differentiation of CD4' CTL. In order to address this issue, we examined the influences of some factors on the generation of CD4' CTL specific to mycobacterial antigens. After 7 days' stimulation of PBMCs from healthy tuberculin reactors with mycobacterial antigens, the cytolytic activity of purised CD4' T cells toward autologous macrophages infected with mycobacteria was measured by Cr release assay. First, we found that both of live M. tubeiculosis and soluble antigens (ST-CF) induced the cytolytic activity of CD4' T cells, although the inducibility of the former was slightly greater than the latter. Second, the cytolytic activity was maximally induced at the relatively low antigen concentration (0.2:1 bacteria:monocyte ratio or 0.5 mg/ml of ST-CF). Finally, in the presence of increasing amounts of neutralizing anti-IL-12 or anti-IFN-r MoAb, the cytolytic activity of CD4+ T cells was decreased in a dose-dependent manner. These results suggest that low dose of antigen, its particulate type give mycobacteria), IL-12, and IFN-r give some positive signals for the generation of CD4+ CTL.
Humans ; Interleukin-12 ; Macrophages ; T-Lymphocytes* ; Tuberculin

In this study, we compared two different tumor cell vaccines for their induction of anti-tumor immunity; one was a tumor cell clone expressing a membrane-bound form of IL-12 p35 subunit (mbIL-12 p35 tumor clone), and the other was a tumor clone expressing heterodimeric IL-12 as a single chain (mb-scIL-12 tumor clone). The stimulatory effect of mb-scIL-12 on the proliferation of ConA-activated splenocytes was higher than that of mbIL-12 p35 in vitro. However, the stimulatory effect of mbIL-12 p35 was equivalent to that of recombinant soluble IL-12 (3 ng/ml). Interestingly, both tumor clones (mbIL-12 p35 and mb-scIL-12) showed similar tumorigenicity and induction of systemic anti-tumor immunity in vivo, suggesting that tumor cell expression of the membrane-bound p35 subunit is sufficient to induce anti-tumor immunity in our tumor vaccine model.
Clone Cells ; In Vitro Techniques ; Interleukin-12* ; Vaccines

No abstract available.
Dermatitis, Atopic* ; Histamine* ; Humans ; Interleukin-12*

No Abstract Available.
DNA* ; Interleukin-12* ; Mycobacterium tuberculosis* ; Mycobacterium*

In the present study we evaluated the anti-inflammatory potential of 3-hydroxy-4,7-megastigmadien-9-one (Comp) isolated from Ulva pertusa Kjellman, in LPS-stimulated bone marrow-derived dendritic cells (BMDCs). Comp treatment exhibited strong dose dependent inhibition of IL-12 p40 and IL-6 cytokine production with IC₅₀ values of 7.85 ± 0.32 and 7.86 ± 0.18, respectively in LPS-stimulated BMDCs. Treatment of Comp inhibited MAPKs and NF-κB pathways in LPS-stimulated BMDCs by inhibiting the phosphorylation of ERK1/2, JNK1/2, p38 and IκB. Thus, these results suggest that Comp have a significant anti-inflammatory property and affirm further studies concerning the potentials of Comp for medicinal use.
Dendritic Cells ; Interleukin-12 ; Interleukin-6 ; Phosphorylation ; Protein Kinases* ; Ulva*

OBJECTIVE: To investigate the characteristic changes of the plasma cytokine profile in Chinese patients with idiopathic multicentric Castleman diseases (iMCD). METHODS: The plasma samples from 22 patients with confirmed diagnosis of iMCD were collected before treatments; Specimens from 17 patients with newly diagnosed multiple myeloma, 10 non Hodgkin's lymphoma, and 15 healthy donors were used as control. Seventeen kinds of cytokines were measured by cytokine beads array (CBA) and ELISA respectively. RESULTS: Six cytokines were measured by ELISA. The concentrations of IL-2, IL-6, IL-21 and VEGF were significantly higher in the plasma of iMCD patients than those of the healthy donors (P＜0.01) and the level of IL-21 was highest in the iMCD group. There was no significant difference in the levels of IL-1β and IL-4 between the iMCD and healthy donor groups. Thirteen cytokines were measured by CBA assay, besides IL-6 level was confirmed to be higher in iMCD group than that in healthy controls (P＜0.01）, IL-12-p70 and IL-33 levels were also higher in iMCD group than those in control group (P＜0.05）, no significant difference of the rest cytokines was found between iMCD and the control group. CONCLUSION IL-6 and VEGF has shown to involved in the pathogenesis of iMCD, the results of preliminary study imply the role of IL-2 、IL-21、IL-12-p70 and IL-33 in this rare lymphoproliferative disease. Further studies are needed to elucidate the mechanism of these cytokines, which may shed some light on the identification of novel therapeutic targets against iMCD.
Castleman Disease ; Cytokines ; Humans ; Interleukin-12 ; Interleukin-1beta ; Plasma

Interleukin 12 (IL-12), a heterodimeric cytokine, promotes an effective antitumor response against tumors of various histological types when delivered systemically as a protein or locally by gene transfer. We investigated parameters that influenced the effectiveness of IL-12 retroviral-mediated gene therapy of cancer in animals using the murine breast cancer line TS/A. Syngeneic fibroblasts (TIB80), stably transduced with a retrovirus expressing murine IL-12, were used for peritumoral injection. Injection of fibroblasts into established tumors resulted in complete regression of tumor in 40 % of animals in a dose dependent manner when treated on day 4, and 20 % when treated on day 8. Significant inhibition of growth of day 21 and day 40 tumors was observed following peritumoral injection of IL-12-expressing fibroblasts in a dose-dependent manner. Delivery of IL-12 by syngeneic fibroblasts at a tumor site is effective in eradicating established, weakly immunogenic TS/A tumors.
Animals ; Breast Neoplasms ; Fibroblasts ; Genetic Therapy* ; Interleukin-12* ; Retroviridae

BACKGROUND: In addition to TCR and costimulatory signals, cytokine signals are required for the differentiation of activated CD8 T cells into memory T cells and their survival. Previously, we have shown that IL-12 priming during initial antigenic stimulation significantly enhanced the survival of activated CD8 T cells and increased the memory cell population. In the present study, we analyzed the mechanisms by which IL-12 priming contributes to activation and survival of CD8 T cells. METHODS: We observed dramatically decreased expression of CD43 in activated CD8 T cells by IL-12 priming. We purified CD43(lo) and CD43(hi) cells after IL-12 priming and analyzed the function and survival of each population both in vivo and in vitro. RESULTS: Compared to CD43(hi) effector cells, CD43(lo) effector CD8 T cells exhibited reduced cytolytic activity and lower granzyme B expression but showed increased survival. CD43(lo) effector CD8 T cells also showed increased in vivo expansion after adoptive transfer and antigen challenge. The enhanced survival of CD43(lo) CD8 T cells was also partly associated with CD62L expression. CONCLUSION: We suggest that CD43 expression regulated by IL-12 priming plays an important role in differentiation and survival of CD8 T cells.
Adoptive Transfer ; Granzymes ; Interleukin-12 ; Memory ; T-Lymphocytes