IL-1beta induces alkaline phosphatase in human phagocytes.

BACKGROUND: Alkaline phosphatase (ALPase) is found in blood plasma or serum and leukocytes and regulates intercellular processes, maintaining phosphoryl metabolites in a steady state, as well as synthesizing and hydrolyzing phosphate esters on membranes. ALPase supervises the active transport of inorganic phosphates, fats, proteins, carbohydrates and the sodium/potassium pump mechanisms. The formed elements of blood such as polymorphonuclear (PMNs) leucocytes, macrophages (MP) and some lymphocytes are high in ALPase concentrations. METHODS: In this study we have tested whether the interleukin-1 receptor antagonist (IL-lra) could influence ALPase generation in IL-1beta or lipopolysaccharide (LPS)-stimulated neutrophils and MP. Human neutrophils were isolated from heparin-anticoagulated blood drawn from healthy individuals by centrifugation in a two-step gradient, Ficoll-Hypaque. ALPase activity was assessed spectrophotometrically in test tubes containing isolated neutrophils and adherence PBMCs treated with LPS, IL-1beta and IL-1ra, alone or in combination. RESULTS: IL-lbeta or LPS enhanced ALPase in both PMNs and MP, whereas IL-1ra could not inhibit ALPase activity. We performed time course experiments at 0 min, 5 min, 1 h, 24 h, and 43 h (LPS 20 microg/mL, IL-1beta 10 ng/mL). No significant increase in ALPase activity was seen until 1 h; however, there was a rapid rise over the next few hours. In another set of experiments using IL-1ra (500 ng/mL), there was no difference between treated cells and control cells. The combination of IL-1beta plus IL-1ra did not reduce the ability of IL-1beta to induce ALPase activity. CONCLUSIONS: These data suggest that IL-1beta stimulates ALPase through other mechanisms than the release of arachidonic acid products, which are inhibited by IL-lra.

Role of mast cells in tumor growth.

The growth of malignant tumors is determined in large part by the proliferative capacity of the tumor cells. Clinical observations and animal experiments have established that tumor cells elicit immune responses. Histopathologic studies show that many tumors are surrounded by mononuclear cell and mast cell infiltrates. Mast cells are ubiquitous in the body and are critical for allergic reactions. Increasing evidence indicates that mast cells secrete proinflammatory cytokines and are involved in neuro-inflammatory processes and cancer. Mast cells accumulate in the stroma surrounding certain tumors, especially mammary adenocarcinoma, and the molecules they secrete can benefit the tumor. However, mast cells can also increase at the site of tumor growth and participate in tumor rejection. Mast cells may be recruited by tumor-derived chemoattractants and selectively secrete molecules such as growth factors, histamine, heparin, VEGF, and IL-8, as well as proteases that permit the formation of new blood vessels and metastases. Tumor mast cell intersections play regulatory and modulatory roles affecting various aspects of tumor growth. Discovery of these new roles of mast cells further complicates the understanding of tumor growth. This review focuses on the strategic importance of mast cells to the progression of tumors, and proposes a revised immune effector mechanism of mast cell involvement in tumor growth.

IL-10, an inflammatory/inhibitory cytokine, but not always.

IL-10 has been previously called cytokine synthesis inhibiting factor, produced mostly by Th2 cells, macrophages and CD8+ cell clones. IL-10 is capable of inhibiting the synthesis of several cytokines from different cells, antigen or mitogen activated. IL-10 exerts its inhibition at the mRNA transcriptional and translational level. In addition, IL-10 is a co-stimulatory cytokine on activated T cells. For example, IL-10 inhibits NK cell activity, the production of Th1 cytokines, cytokines generated by peripheral blood mononuclear cells, and macrophage activity. On the other hand, IL-10 exerts immunostimulatory effects on B cells, cytotoxic T cell development and thymocytes. In mast cells derived from CD4+/CD133+ cells, IL-10 inhibits IL-6 and TNFalpha, and prostaglandin E(1) and E(2) induced by IL-6. Here, we report for the first time that IL-10 fails to inhibit tryptase and IL-6 from human mast cell-1 (HMC-1) and human umbilical cord blood-derived mast cells.

Expression and secretion of CXCL8 (IL-8), release of tryptase and transcription of histidine decarboxylase mRNA by anti-IgE-activated human umbilical cord blood-derived cultured mast cells.

Activation of cytokine receptors and alterations in cytokines are thought to play important roles in neuronal dysfunction and in the pathogenesis of the nervous system diseases. CXCL8 (IL-8) is a CXC chemokine with chemotactic and inflammatory properties. Chemokines control mast cell infiltration in several inflammatory diseases, including stress and neurological dysfunctions. Using isolated human umbilical cord blood-derived cultured mast cells (HUCMC) from hematopoietic stem cells CD34+, mast cells were immunologically activated with anti-IgE at concentrations of 1, 5, 10 and 20 microg/ml leading to the dose-dependent production of IL-8 (p < 0.05). The increase in IL-8 mRNA expression was also noted when the cells were treated with anti-IgE at 10 microg/ml for 6 h. Immunologically activated HUCMC provoked the generation of tryptase in a dose- and time-dependent manner. We also found increased histidine decarboxylase (HDC) expression in activated HUCMC after 6 h of incubation, a rate-limiting enzyme responsible for the generation of histamine from histidine. Taken together, these results confirm that anti-IgE-activated mast cells release inflammatory mediators including CXCL8, a CXC chemokine which regulates several biological effects of mast cells, e.g. chemoattraction, and possibly causes cell arrest.

Interleukin-16 network in inflammation and allergy.

Interleukin (IL)-16 is a homotetramer of 14-kDa subunits discovered in 1982 as a T-cell-specific chemoattractant factor. IL-16 plays a role in trafficking of several immune cells and may be a major chemotactic signal for CD4+ cells. Here, we review some of the key biological actions of IL-16. Because this cytokine has been shown to affect the levels of many inflammatory mediators such as histamine, serotonin, regulated upon activation, normal T cell expressed and secreted (RANTES), and monocyte chemotactic protein-1 (MCP-1), and other cytokines such as IL-2, we investigated the effect of IL-16 on control and stimulated human umbilical cord blood-derived cultured mast cells after antigen challenge. We found that human recombinant IL-16 (0.2-200 ng/mL) does not affect either basal tryptase or IL-8 release or that induced by anti-immunoglobulin E activation. In accordance with other data in the medical literature, we conclude that the most important function of IL-16 is the chemoattraction of CD4+ cells.