Cytokines, mononuclear cell

Wetzel MA, Steele AD, Eisenstein TK, Adler MW, Henderson EE, Rogers TJ (2000) Mu-opioid induction of monocyte chemoattractant protein-1, RANTES, and IFN-gamma-inducible protein-10 expression in human peripheral blood mononuclear cells. J Immunol 165 6519-6524 Widmer U, Manogue KR, Cerami A, Sherry B (1993) Genomic cloning and promoter analysis of macrophage inflammatory protein (MIP)-2, MIP-1 alpha, and MIP-1 beta, members of the chemokine superfamily of proinflammatory cytokines. J Immunol 150 4996-5012 Ye RD (2001) Regulation of nuclear factor kappaB activation by G-protein-coupled receptors. [Review] [136 refs]. J Leukoc Biol 70 839-848... 

Peterson PK, Sharp BM, Gekker G, Jackson B, Balfour HH Jr (1991) Opiates, human peripheral blood mononuclear cells, and HIV. Adv Exp Med Biol 288 171-178 Peterson PK, Gekker G, Schut R, Hu S, Balfour HH Jr, Chao CC (1993) Enhancement of HlV-1 replication by opiates and cocaine the cytokine connection. Adv Exp Med Biol 335 181-188 Peterson PK, Gekker G, Hu S, Sheng WS, Molitor TW, Chao CC (1995) Morphine stimulates phagocytosis of Mycobacterium tuberculosis by human microglial cells involvement of a G protein-coupled opiate receptor. Adv Neuroimmunol 5 299-309 Peterson PK, Molitor TW, Chao CC (1998) The opioid-cytokine connection. J Neuroimmunol 83 63-69... 

Findings from studies of schistosomiasis-induced liver fibrosis, as well as other models of pulmonary, kidney, and liver fibrosis, strongly support the role of CD4+ Th2 cells in the progression of fibrosis (4). In this regard, analyses of gene and protein expression after stimulation by Thl (vs. Th2) cytokines indicates that IL-4 is found at increased concentrations in the bronchoalveolar lavage (BAL) fluid of patients with idiopathic pulmonary fibrosis, as well as in the peripheral blood mononuclear cells of those afflicted with periportal fibrosis (10,53-56). 

The CXC chemokines can be divided into two groups on the basis of a structure/function domain consisting of the presence or absence of three amino acid residues (Glu-Leu-Arg ELR motif) that precedes the first cysteine amino acid residue in the primary structure of these cytokines. The ELR+ CXC chemokines are chemoattractants for neutrophils and act as potent angiogenic factors (6). In contrast, the ELR" CXC chemokines are chemoattractants for mononuclear cells and are potent inhibitors of angiogenesis (Table 1) (6). 

Fig. 11.1. Atherogenesis is a persistent inflammatory response that occurs in response to conditions that cause endothelial damage (e.g., hypercholesterolemia and oxLDL). After endothelial cells are activated, they elaborate cytokines, chemokines, and other mediators that recruit mononuclear cells (monocytes and T lymphocytes) to extravasate into the vessel wall where they are activated and release additional proinflammatory factors. Macrophages are able to take up oxLDL via scavenger receptors causing them to differentiate into foam cells and form a fatty streak that progresses to an atheroma with a necrotic lipid core and a fibrous cap. Chemokines can lead to weakening of the fibrous cap and eventual plaque rupture leading to thrombosis and occlusion of the involved vessel.

Interferon-y (IFN-y) mRNA levels were measured in unstimulated peripheral blood mononuclear cell (PBMC) and purified cell populations, using a bDNA assay, to characterize the cell types that contribute to the in vivo increase in IFN-y gene expression seen in HIV infection (Breen et al 1997). IFN-y is a cytokine that can be produced by multiple cell types and is considered to enhance cellular responses by activation of monocytes and macrophages. It is one of the type 1 cy-... 

As a consequence of the various approaches adopted in naming and classifying cytokines, it is hardly surprising to note that many are known by more that one name. IL-1, for example, is also known as lymphocyte activating factor (LAF), endogenous pyrogen, leukocyte endogenous mediator, catabolin and mononuclear cell factor. This has led to even further confusion in this field. 

Pacifici R, Brown C, Puscheck E, Friedrich E, Slatopolsky E, Maggio D, McCracken R, Avioli LV (1991) Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. Proc Nad Acad Sci USA 88 5134-5138... 

Pisa, E.K. et al., OKT3-induced cytokine mRNA expression in human peripheral blood mononuclear cells measured by polymerase chain reaction, ScandL J. Immunol., 36, 745, 1992. 

To characterize IRIV-elicited immune responses in vitro, we addressed cell proliferation and cytokine expression in peripheral blood mononuclear cell (PBMC) cultures, as well as IRIV effects on dendritic cells (DC). In all experiments, PBMC were obtained from healthy donors and, if needed, further separated into different cell subsets. Finally, cells were cultured in the presence or absence of IRIV as indicated. 

Figure 2 Cytokine gene expression in immunopotentiating reconstituted influenza virosomes (IRIV) stimulated peripheral blood mononuclear cells (PBMC). PBMC were cultured in the presence or absence of IRIV. On days 1 and 2, culture cells were harvested and total cellular RNA was extracted and reverse transcribed. The cDNAs thus obtained were tested in real time polymerase chain reaction assays in the presence of primers specific for the indicated cytokine genes. Source From Refs. 6 and 9.

Figure 3 Cytokine secretion in immunopotentiating reconstituted influenza viro-somes (IRIV)-stimulated peripheral blood mononuclear cells (PBMC). PBMC from a healthy donor were cultured in the absence of stimuli (Neg) or in the presence of IRIV (V, 1 50 diluted) or control liposomes (L, 1 50 diluted). On days 1, 2, and 4 supernatants were harvested and the concentrations of interferon-y (A), GM-CSF (B), TNF-a (C), and interleukin-4 (D) were determined by ELISA. Abbreviations GM-CSF, granulocyte monocyte colony stimulating factor TNF-a, tumor necrosis factor-a. Source From Ref. 6.

Other early work includes that of Moody et al. (2001) who spotted anticytokine monoclonals onto the bottom of polystyrene microtiter plates (Max-isorp, Nalge Nunc) and measured cytokine levels in stimulated peripheral blood mononuclear cells. Finally, although not strictly a microarray, the microwell array system developed by Michael Snyder s group at Yale University to measure kinase activity is a simple and elegant approach (Zhu et al., 2000). The "protein chip" is comprised of microwells fabricated in a flexible elastomer of PDMS [poly(dimethylsiloxane)] substrate by a molding process. 

Hawkes, J. S., Bryan, D. L., and Gibson, R. A. (2002). Cytokine production by human milk cells and peripheral blood mononuclear cells from the same mothers. /. Clin. Immunol. 22, 338-344. 

IL-10 A cytokine inhibitory factor synthesized by TH2 cells, macrophages, and B cells. IL-10 inhibits the formation of inflammatory cytokines. Its synthesis is most reliably determined by means of IL-10 mRNA expression in mononuclear cells. 

T-cells influence. SSTE and nicotine were incubated in splenic mononuclear cells at concentrations of 1 10 or 1 10 dilutions of STD, or 10 or 100 i.g/mL nicotine, during 4 days of stimulation with anti-CD3. The treatment sustained expression of IL-2, IFN-y, IL-10, and IL-4 cytokine mRNA at 100 i.g/mL nicotine. STD did not exhibit residual expression of cytokine mRNA. Restimulated STD exhibited maximum IL-2, IL-4, IFN- y, and IL-10 mRNA at 48 hours . STE, in splenic mononuclear cell culture at LlOHo 1 10 dilutions, increased IL-2 production and decreased IL-10 at 1 10 dilution. IFN-y production was decreased at all concentrations. STE did not alter IL-4 product ion k P-benzoquinone, a thiol-reactive benzene derivative from cigarette tar, was incubated in human peripheral blood mononuclear cells at a concentration of 10 xM. The treat-... 

In 1985 Nerup and co-workers demonstrated that treatment of isolated rat and human islets with conditioned media derived from activated mononuclear cells resulted in the inhibition of glucose-stimulated insulin secretion (Mandrup-Poulsen et cd., 1985). The cytokine IL-1/3 was found to be the active component of the conditioned media (Bendtzen etal., 1986). Mandrup-Poulsen et al. (1986) further showed that continuous exposure of islets to IL-1 is toxic. 

DPDPE has been found to have marked in vitro immunostimulant activity in patients suffering from leprosy and tuberculosis, enhancing antigen-stimulated proliferation of peripheral blood mononuclear cells and T-cell rosetting. DPDPE has been found to enhance cytokine production by T-helper cells, IL-6 production by macrophages and NK cell activity in murine splenocytes, suggesting immunostimulatory activity at low in vitro... 

The studies from our group showed that curcumin inhibited pancreatic cancer in patients. Twenty-five patients were enrolled in this study. Patients received 8 g of curcumin orally daily until disease progression, with restaging every 2 months. Serum cytokine levels for IL-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell (PBMC) expression of NF-kB and COX-2 were monitored. Out of 25 patients, 21 were evaluable for... 

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