Cytokines interactions between

Inflammation. Figure 1 Sequence of events in the recruitment of leukocytes in postcapillary venules adjacent to injured tissue. At the site of lesion, diverse reactive substances stimulate the endothelium to produce inflammatory cytokines, chemoattractants and other inflammatory mediators. The cytokine-activated endothelium expresses adhesion molecules that lead to the low affinity interactions between leukocytes and endothelium, which is mediated by selectins and described as rolling. Subsequently integrins mediate the firm adhesion of leukocytes, which allows emigration of the cells from venules into the interstitial compartment. Activated mast cells, PMNs and macrophages secrete cytokines (TNFa), lipid mediators (LTB4) and other inflammatory players (histamine, NO). 

Sirolimus is currently the only FDA-approved ToR inhibitor. One of its derivatives, everolimus, is in phase III clinical trials and has been approved for use in some European countries.30 Sirolimus is a macrolide antibiotic that has no effect on cal-cineurin phosphatase.11,31,32 Sirolimus inhibits T cell activation and proliferation by binding to and inhibiting the activation of the mammalian ToR, which suppresses cellular response to IL-2 and other cytokines (i.e., IL-4 and IL-15J.11,31 Studies have shown that sirolimus may be used safely and effectively with either cyclosporine or tacrolimus as a replacement for either azathioprine or mycophenolate mofetil.33 However, when using both sirolimus and cyclosporine as part of a patient s immunosuppressant therapy, because of a drug interaction between the two resulting in a marked increase in sirolimus concentrations, it is recommended to separate the sirolimus and cyclosporine doses by at least 4 hours. Sirolimus also can be used as an alternative agent for patients who do not tolerate calcineurin inhibitors due to nephrotoxicity or other adverse events.34... 

Neutrophils are the most abundant leukocytes in humans, comprising about two thirds of peripheral blood leukocytes. Upon tissue injury, they rapidly infiltrate injury sites and play an important role in innate immune responses. In addition, they also contribute to the development of adaptive immune responses by producing an array of cytokines and chemokines. Tissue infiltration of neutrophils is initiated by signals generated by the interaction between chemoattractants produced at sites of injury and their corresponding cell surface receptors. Classical chemoattractants, such as C5a, N-formyl-methionyl-leucyl-... 

Figure 1.9. Interactions between macrophages and T helper cells. Stimulation of T helper cells results in the secretion of yinterferon, which then stimulates macrophages. The y interferon-stimulated macrophages then secrete Interleukin-1, which stimulates the T helper cells to secrete more yinterferon. Thus, a cytokine loop develops.

Due to the complexity and the manifold interactions between cytokines, determination of an optimum cytokine mix for stem cell cultivation is difficult and most optimization algorithms are inefficient. Significant progress can be made using genetic algorithms, as shown by Thoma et al. [41]. 

Muromonab is a mouse monoclonal antibody against the CD3 receptor of T-lymphocytes. Its activity is based on inhibition of interactions between antigen-presenting cells and T-cells. By preventing antigen presentation it suppresses T-cell activation and proliferation. The indication for muromonab is the treatment of acute graft rejection after kidney, liver and hart transplantations. Its adverse effects consist of those symptoms that are initiated by the release of cytokines and lymphokines as a result of the reaction of muromonab with CD3 positive T-lymphocytes. These symptoms may vary from a mild flu-like syndrome to serious cardiac, pulmonale and neurological reactions. 

Cytokine is a general term used for a diverse assortment of water-soluble protein molecules that mediate interactions between the various cells of the innate and adaptive immune systems. Over 100 human cytokines are currently under study and more than 300,000 research papers have been published in this area over the past 10-15 years. The interferons, discussed in section 6.2.1, are a subset of the cytokines, as are the interleukins, discussed in section 6.1.3. The nomenclature used to describe cytokines is somewhat confusing and varying subclasses of cytokines are recognized ... 

A characteristic that significantly differentiates some of the cytokines from other hormones is the coupling of their activity to cell-cell interactions. The function of some cytokines such as the interleukins lL-4, lL-5, lL-6 and lL-10 is closely associated with the interaction between B and T lymphocytes. 

---