Mononuclear cell-stimulating factor

Zhu J, Mix E, Olsson T, Link H (1994) Cellular messenger-Rna expression of interferon-gamma, 11-4 and transforming growth-factor-beta (Tgf-Beta) by rat mononuclear-cells stimulated with peripheral-nerve myelin antigens in experimental allergic neuritis. Clin Exp Immunol 98 306—312. 

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.

R. J. Tushinski and E. R. Stanley, The regulation of mononuclear phagocyte entry into S phase by the colony stimulating factor CSF-1, J.Cell.Physiol. 122, 221-228 (1985). 

Dai, X.M., Ryan, G.R., Hapel, A.J., Dominguez, M.G., Russell, R.G., Kapp, S., Sylvestre, V., and Stanley, E.R. (2002) Targeted Disruption of the Mouse Colony Stimulating Factor 1 Receptor Gene Results in Osteopetrosis, Mononuclear Phagoc34e Deficiency, Increased Primitive Progenitor Cell Frequencies, and Reproductive Defects. Blood99, 111 20. 

Imiquimod (Aldara) is an immunomodulator approved for the treatment of external genital and perianal warts in adults, actinic keratoses on the face and scalp, and biopsy-proven primary basal cell carcinomas on the trunk, neck, and extremities. The mechanism of its action is thought to be related to imiquimod s ability to stimulate peripheral mononuclear cells to release interferon- and to stimulate macrophages to produce interleukins-1, -6, and -8, and tumor necrosis factor- (TNF-k). 

After binding and phagocytosis, alveolar macrophages and monocytes release pro-inflammatory cytokines, e.g. lL-1, interferon-y and tumor necrosis factor-a (fig. 1). These cytokines activate resident cells (epithelial cells, fibroblasts) to produce chemokines such as lL-8, granulocyte-monocyte-colony-stimulating factor, RANTES (regulated on activation normal T cell expressed and secreted) that will result in a second wave of cell recruitment (mononuclear and polymorphonuclear cells). 

Purton LE, Lee MY, Torok-Storb B. Normal human peripheral blood mononuclear cells mobilized with granulocyte colony-stimulating factor have increased osteoclastogenic potential compared to nonmobihzed blood. Blood 1996 87(5) 1802-8. 

Cytokines may also be released after host defense peptide stimulation of several cells. LALF(31-52), a peptide derived from L. polyphemus anti-LPS factor, induced the release of a mixed Thl/Th2 cytokine profile (IFN-a, IFN-y, IL-2 and IL-13) from human peripheral blood mononuclear cells [191], and increased... 

Nakamura, Y., Ozaki, T., Kamgi, T., Kawaji, K., Banno, K., Mild, S., Fujisawa, K., Yasuora, S. and Ogura, T. (1993). Increased granulocyte-macrophage colony-stimulating factor production by mononuclear cells from peripheral blood of patients with bronchial asthma. Am. Rev. Respir. Dis. 147, 87-91. 

Kondo N, Kobayashi Y, Shinoda S, et al Reduced interferon garrrma production by antigen-stimulated cord blood mononuclear cells is a risk factor of allergic disorders - 6 year follow-up study. Clin Exp Allergy 1998 28 1340—1344. (II)... 

The studies mentioned above indicate that bromelain has a certain cytotoxic potential. It remains an open question whether the observed antineoplastic effects of bromelain preparations reside in the proteolytic enzyme or in some or more other components of the mixture. Before the work of Maurer et al. [104] and of Batkin et al. [105], the antitumor activity of bromelain was explained primarily by its fibrinolytic and platelet aggregation inhibitory activity, which is believed to interfere with the fibrin and coagulation features of tumor cells [2], More recently, Desser and Rehberger [107] demonstrated that bromelain stimulates the production of alpha tumor necrosis factor in human peripheral blood mononuclear cell cultures in a time-dependent manner. Immunomodulation, especially the release of cytokines, is believed to be responsible for the possible therapeutic potential of bromelain. However, further experimental evidence is necessary, first, to prove the antineoplastic action of the proteolytic enzyme, and second, to demonstrate that bromelain in vivo is a valuable therapeutic agent in humans. 

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