LPS-induced production

In endotoxinemic mice IL-10 treatment inhibits proinflammatory cytokine release and leads to a reduction in LPS toxicity (G8, H28). IL-10 does not influence the LPS-induced production of IL-6 in vivo (M9). This suggests that IL-10 could differentially regulate TNF and IL-6 production by macrophages in vivo, in contrast to data obtained in vitro (Wl), or that cell types other than macrophages are a major source of IL-6 in vivo and are resistant to IL-10 (S23). 

Rose, P. et al., [i-phcnylcthyl and 8-methylsulphinyloctyl isothiocyanates constituents of watercress suppress LPS induced production of nitric oxide and prostaglandin E2 in RAW 2647 macrophages, Nitric Oxide, 12(4), 237, 2005. 

IL-22. IL-10-related T cell-derived inducible factor (IL-TIF provisionally designated IL-22) is a cytokine distantly related to IL-10 and is produced by activated T cells (D16). IL-22 receptor, a new member of the interferon receptor family, and CRF2-4, a member of the class II cytokine receptor family, join together to enable IL-22 signaling. Cell lines that respond to IL-22 by activation of STATs 1,3, and 5, but unresponsive to IL-10, have been identified (XI). In contrast to IL-10, IL-22 does not inhibit the LPS-induced production of proinflammatory cytokines by monocytes, but it has a modest inhibitory effect on IL-4 production from Th2 cells (XI). 

Tomozawa et al. (Tomozawa et al., 1995) showed that isoproterenol induces IL-1 (3 mRNA in microglia, but not in astrocytes. This increase was inhibited by propranolol and by a cAMP-dependent protein kinase inhibitor. Similarly, NE, (31- and (32-adrcnorcccptors agonists produce an increase in IL-1 (3 mRNA, which is suppressed by (3i- and (32-adrenoreceptors antagonists (Tanaka et al., 2002). In line with those data, isoproterenol increases IL-la and IL-1 (3 mRNA in microglia (Hetier et al., 1991). On the other hand, these authors also showed that LPS-induced production of IL-1 P protein was inhibited by isoproterenol (Hetier et al., 1991). NE also decreases the production of IL-1(3 induced by LPS in miroglia (Dello Russo et al., 2004) (Madrigal et al., 2005). However, the reasons for these differences among the studies are still not clear. 

Essential oils have also been shown to be useful as anti-inflammatory agents. The anti-inflammatory and antipyretic activities of Ocimum sanctum fixed oil have been evaluated recently [220]. The results reported are consistent with the folk medicine use of different parts of this plant for the treatment of acute and chronic inflammation. The results of an investigation on the anti-inflammatory activities of flavonoids of Baphia nitida, another plant used in folk medicine, were recently reported [221]. The flavo no id-rich fraction of the leaf, obtained by a chromatographic process, was formulated into an ointment and exhibited significant antiinflammatory activity in several rodent inflammation models. The inhibition of tumor necrosis factor (TNF-a) and interleukin-1(3 (IL-1), mediators in many acute and chronic inflammatory diseases, by curcumin (111), a phytochemical isolated from the plant Curcuma longa Linn, was recently reported [222]. This report shows that, in vitro, curcumin (111), at 5 (J.M, inhibited lipopolysaccharide (LPS)-induced production of TNF-a and IL-1 by a human monocytic macrophage cell line. 

Astragalus mongholicus Bunge Fabaceae Inhibit LPS-induced production of TNF-a and L-8 [147]... 

Bupleurum smithii var. parvifolium Ammineae Enhance phagocytic functions of macrophages, inhibited LPS-induced productions of NO, and proinflammatory cytokines [148]... 

Conforti, F., Menichini, R, Formisano, C., Rigano, D Senatore, F Bruno, M. et al. (2012). Anthemis wiede-manniana essential oil prevents LPS-induced production of NO an RAW 264.7 macrophages and exerts antiproliferative and antibacterial activities in vitro. N L, S2dhM d- 26(17), 1594-1601. 

The anti-inflammatory effect of the EO of the Myrtaceae Melaleuca altemifolia (TTO) was evaluated by Hart et al. (2000). The authors tested the ability of TTO to inhibit the production of inflammatory mediators such as the TNF-a, IL-ip, IL-8, IL-10, and the PGE2 by LPS-activated human peripheral blood monocytes. A toxic effect on monocytes was achieved at a concentration of 0.016% vol/vol by TTO anulsilied by sonication in a glass tube into culture medium containing 10% fetal calf serum (PCS). In addition, a significant suppression of LPS-induced production of TNF-a, IL-ip and lL-10 (by approximately 50%), and PGE2 (by approximately 30%) after 40 h could be observed with the water-soluble components of TTO at a concentration equivalent to 0.125%. The main constituents of this EO were terpinen-4-ol (42%), a-terpineol (3%), and 1,8-cineole (2%). When tested individually, only terpinen-4-ol inhibited the production of the inflammatory mediators after 40 h. 

The structure-activity relation of triterpene QMs on the anti-inflammatory effect has been investigated with a series of analogues by comparing inhibition of the IL-1 (3 production in the LPS-induced monocytes.93-94 Clearly, the conjugated QM structure with alkenes is essential for the observed inhibition, and similar inhibitory effect was found with derivatives that are capable to form the conjugated QM through hydrolysis and/or oxidation.93-94 Also, the presence of the E ring in the triterpene QM structure is an additional contributor. 

DL-10 (35) T cell, fibroblast Suppression of B- and T-cell proliferation. Inhibition of LPS-induced monocyte IL-1, IL-8, and TNF production. Induction of IL-lra. Suppression of free radical release and NO-dependent microbicidal activity of macrophages. 

Chlorpromazine (CPZ) and pentoxifylline (PTX) were shown to inhibit TNF release and improve survival during murine endotoxemia (Gl). CPZ (M25) and epinephrine (PI6) pretreatment markedly up-regulated IL-10 production induced by LPS, a phenomenon also observed with cyclosporine (Dl). PTX pretreatment did not affect LPS-induced IL-10 release. Thus, TNF and IL-10 can be differentially regulated during murine endotoxemia. The sustained or even increased production of IL-10 could play a role in the protective effects of these drugs against LPS toxicity in vivo. 

Mature B lymphocytes express AhR and ARNT,10,12 and the ability of TCDD to suppress primary antibody responses has been known for a long time (reviewed in4). While the precise mechanisms resulting in suppression of T-dependent B cell responses in vivo have not been fully elucidated, it is clear that direct effects of TCDD on B cells plays a role. Studies using two B cell lines with differential AhR expression have linked suppression of LPS-induced IgM production to AhR activation, and have shown that AhR interactions within the 3 alpha immunoglobulin heavy chain enhancer directly influence antibody production.52-54 TCDD also appears to directly modulate the expression of CD19 on human B cells, suggesting another mechanism by which TCDD down-modulates the responsiveness of mature B cells.55... 

Diphenylhydantoin, which has been demonstrated to cause autoimmune phenomena in man (SLE, vasculitis and scleroderma and skin) has also been tested (via drinking water for 6 months) in genetically predisposed mice (C57BL/6-lpr/lpr strain) but the compound depressed rather than increased the levels of ANA (55 and section 4.1, below). In another study [56], a slight shift towards a Th2 response was demonstrated as an increase in the KLH-induced production of IL-4 and IgE (IgE was detected by direct ELISA, which makes these data suspect) in a 4 weeks exposure study. In this same study, proliferative responses of splenocytes to KLH (using spleen cells of KLH-sen-sitized mice), mitogens (ConA, LPS) or anti-CD3 were also reduced, possibly through interference with accessory cell function. 

In addition to directly eliciting cell chemotaxis and free-radical production, PAF can also induce the release of various inflammatory cytokines, amongst which tumour necrosis factor (TNF) is of particular importance [ 312 ]. We have recently shown that PAF stimulates TNF production from peripheral blood derived monocytes and at picomolar concentrations amplifies lipopoly-saccharide (LPS)-induced TNF production, effects inhibited by various PAF antagonists [313]. PAF also acts synergistically with interferon-y (IFN-y) to increase the monocyte cytotoxicity. Furthermore, PAF can modulate the production of both interleukin 1 and interleukin 2 (IL-1, IL-2) from rat monocytes and lymphocytes, respectively [222, 223], cytokines which in turn elicit the release of other mediators and growth factors. 

---