Natural killer cells, stimulation

Munakata T, Semba U, Shibuya Y, et al Induction of Interferon-gamma Production by Human Natural Killer Cells Stimulated by Hydrogen Peroxide. J. Immunol. 1985 134(4) 2449-2455. 

Borish L. IL-10 evolving concepts. J Allergy Clin Immunol 1998 101 293-297. Manetti R, Parronchi P, Giudizi M, et al. Natural killer cell stimulating factor (Interleukin-12) induces T helper type l(Th)-speciflc immune responses and inhibits the development of IL-4 producing Th cells. J Exp Med 1993 177 1199-1204. 

TNF (17.5) Monocyte/macrophage, lymphocyte, neutrophil, endothelium, fibroblast, keratinocyte Activation of T and B cells, natural killer cells, neutrophils, and osteoblasts. Stimulation of endothelial cells to release chemotactic proteins, NO and PGI2. Tumoricidal activity. Induces fever, sleep, hepatic acute phase protein synthesis, catabolism, ACTH release. Lead to myocardial depression, hypotension/shock, hypercoagulability, and death. Stimulates production of IL-1, IL-6, IL-8, IFN-y, and H202. Suppression of cytochrome P-450, thyroglobulin, and lipoprotein lipase. Induces complement activation, release of eicosanoids, including PAF. Procoagulant activity. 

Several cytokines have been characterized at the molecular level in different species of marine mammals (Table 23.2). In addition, limited evidence exists for conserved functionality of cytokines in marine mammals, such as the ability of human recombinant IL-2 to stimulate T cell proliferation [32, 33] and natural killer cell activity [39,40] in beluga whales and harbor seals. Assays were developed to quantify circulating levels of cytokines [41,42], as well as C-reactive protein, a marker of acute inflammation [43],... 

An alternative mechanism is based on non-complement dependent cytotoxicity, e.g., food allergen stimulation of mechanisms of antibody dependent cellular cytotoxicity (ADCC), cytotoxicity of natural killer cells or macrophages. The contribution of ADCC in gastroenteropathy of children induced by cow s milk allergens was demonstrated by Owen et al. (1993). 

The potential of immunocytokines was elegantly demonstrated in two separate studies using IL-12 for anti-tmnour therapy. IL-12, a potent stimulator of natural killer cells and cytotoxic T-lymphocytes (CTL), activates the immune system to eradicate the cancer cells. IL-12... 

Thymosin is an immunomodulatory peptide produced by the thymus gland and other cells. Thymosin alfa 1, a 28-amino acid peptide, is one member of the family of thymosins that collectively appear to influence a variety of regulatory and counter-regulatory functions in terms of T-cell maturation and antigen recognition, stimulation of native interferons and cytokines such as interleukin-2, and activity of natural killer cell-mediated cytotoxicity. In some countries it is approved as an adjuvant for influenza vaccine or as a treatment for chronic hepatitis B and, in combination with interferon for hepatitis C. Thymosin alfa 1 has been used with some success to treat children with the severe form of Di-George Syndrome. 

Bacillus Calmette-Guerin (BCG) is a viable attenuated strain of Mycobacterium bovis. Nonviable strains of the bacterium also have been shown to augment the immune response. The smallest active compound derived from BCG thus far has been identified as muramyl dipeptide. The T cell is a principal target for BCG. It also appears to stimulate natural killer cells, which in turn can kill malignant cells. It has been suggested that BCG cross-reacts immunologically with tumor cell antigens. 

Williams, B. A. Blay, J. Hoskin, D. W. 2-chloroadenosine stimulates granule exocytosis from mouse natural killer cells Evidence for signal transduction through a novel extracellular receptor. Exp. Cell Res. 1997, 233, 187-197. 

The most relevant bioassays measure specific activities on immune function, either as effector or regulatory, for example, assay of cytokine IL-12 by the augmentation of the cytolytic function of natural killer cells (B9), IL-10 by the inhibition of the production of TNF-o from stimulated monocytes (B13), and IL-8 and eotaxin by the chemotaxis of neutrophils and eosinophils, respectively (C2). 

B9. Bermudez, L. E., Wu, M., and Young, L. S., Interleukin- 12-stimulated natural killer cells can activate human macrophages to inhibit growth of Mycobacterium avium. Infect. Immun. 63, 4099-4104 (1995). 

Furthermore, mouse model against Ehrlich s ascites tumour (EAT) [36]. This study showed that the treatment with ama-titano-cene 48 increases the lifespan of EAT-bearing mice from 25% to around 50% in a dose-dependent manner, and myelopoiesis (the formation of bone marrow or of blood cells derived from bone marrow) was not suppressed. Additionally, these experiments showed that ansa-titanocene 48 restores the natural killer cell function, which is reduced due to a dysfunction in EAT, and stimulates the natural killer cell-mediated cytotoxicity. 

The molecular mechanisms underlying the anticancer effect of InsPg are not understood. Proposed mechanisms of action for InsP are (i) increase in natural killer cell activity and enhanced host immunity, (ii) alteration in signal transduction, (iii) stimulation of genes toward greater cell differentiation, (iv) reduction in cell proliferation, and (v) antioxidant activity (Fox and Eberl, 2002). 

---