Macrophages, human, nitric oxide

Recently, the possibility to use C60 as anti-inflammatory compound has been reported (Huang et al., 2008). Fullerene-xanthine hybrids have been studied to determine if nitric oxide (NO) and tumor necrosis factor-alpha (TNF-a) production in lipopolysaccharide (LPS)-activated macrophages can be inhibited by hybrid administration, finding positive results. The presence of xanthine moiety seems to be essential for the inhibition of LPS-induced TNF-a production, while the fullerene portion ameliorates the efficiency in LPS-induced NO production blockage, leading to a new promising class of potent anti-inflammatoiy agents. It is necessary to mention also the opposite results obtained by an amino acid fullerene derivative tested on human epidermal keratinocytes at concentration from 0.4 to 400 pg/mL. 

We believe that the /3 cell is a source of nitric oxide production by human islets because (1) IL-1 and IFN-induced nitric oxide production by human macrophages has not been clearly demonstrated (2) the cytokine combination of IL-1, IFN, and TNF induces the formation of nitric oxide by human islets either freshly isolated or cultured for 7 days at 25°C (a procedure which removes 80-90% of nonendocrine cells from the islet) and also by islets cryoperserved and (3) NADPH—diaphorase staining reveals that approximately 60-70% of human islet cells treated with cytokines stain for NADPH-diaphorase (J. A. Corbett and M. L. McDaniel, unpublished data). TTiis staining procedure has been shown to colocalize with nitric oxide synthase in a number of cells including rat islets (Corbett et al., 1993c), and nitric oxide synthase has been demonstrated to contain NADPH-diaphorase enzymatic activity (Dawson et al., 1991 Hope et... 

Munoz-Fernandez, M. A., Fernandez, M. A., and Fresno, M. (1992). Activation of human macrophages for the killing of intracellular Trypanosoma cruzi by TNF-alpha and IFN-gamma through a nitric oxide-dependent mechanism. Immunol. Lett. 33, 35-40. 

Activated macrophages and microglia are likely cellular sources of IL-1 in the central nervous system. IL-la and p, both 17-kDa proteins, are the products of two distinct genes and produce many of the same effects that TNF has on glial cells. IL-1 upregulates cytokine production, includes cell surface molecules, activates nitric oxide, and stimulates proliferation. When used alone, IL-1 and TNFa both stimulate nitric oxide production in C6 cells. However, in human fetal astrocyte cultures, IL-1 is a better nitric oxide inducer when used in combination with IFNy. 

Bisphosphonates (particularly clodronate) have been shown to have anti-inflammatory effects in animal models of rheumatoid arthritis (RA), as well as in arthritis in humans. In adjuvant- and antigen-induced arthritis in rats, clodronate suppresses the inflammatory articular lesions in the inflamed joints [29], whilst in human RA, clodronate decreases the levels of interleukin (ILJ-1, tumor necrosis factor-alpha (TNFaand /1-microglobulin in the circulation [30]. In vitro, clodronate inhibits cytokine and nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in macrophage-like cells. 

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