Lymphokine release

A macrophage chemotactic factor (MAC) which causes an aeeumulation of mononuclear phagoeytes at the site of the antigen-mediated lymphokine release. 

Hermann, C. et al., A model of human whole blood lymphokine release for in vitro and ex vivo use, J. Immunol. Methods, 275, 69, 2003. 

Since cellular immunity results in the release of chemotactic lymphocytes that in turn enhance phagocytosis, a deficiency in cellular immunity may also result in chronic infections. Cellular immunity is mediated by T cells, macrophages, and NK cells involved in complex compensatory networks and secondary changes. Immunosuppressive agents may act directly by lethality to T cells, or indirectly by blocking mitosis, lymphokine synthesis, lymphokine release, or membrane receptors to lymphokines. In addition, cellular immunity is involved in the production and release of interferon, a lymphokine that ultimately results in blockage of viral replication (Table 15.4). Viruses are particularly susceptible to cytolysis by T cells since they often attach to the surface of infected cells. Thus, immunosuppression of any of the components of cellular immunity may result in an increase in protozoan, fungal, and viral infections as well as opportunistic bacterial infections. 

To initiate a T-cell immune response, antigen presenting cells have to display antigenic peptides com-plexed with the major histocompatibility complex (MHC) on their cell surface. The T-cell receptor of CDS cells is specific for the peptide-MHC class I complex while the CD4 cell receptor binds the peptide-MHC class II complex. This binding of the peptide-MHC II complex stimulates CD4 cell proliferation and subsequent lymphokine release. This CD4 cell response can initiate a delayed hypersensitivity reaction. However CD4 activation and the production of various lymphokines is also needed for the generation of cytotoxic T-cells and for the differentiation of plasma cells from B-lymphocytes and the antibody response by these plasma cells. For their role in also the humoral immune response CD4 cells are called T-helper cells. 

Rosentein et al. [21] injected high dose IL-2 into mice followed by intravenous bovine serum albumin as a marker of capillary leak. The severity of the vascular leak syndrome was dependent upon the number of days of treatment and the dose given. Severity could be reduced by immune suppression with cyclophosphamide, corticosteriods, or whole body irradiation implying that lymphokines released by lymphocytes placed a role in the induction of the vascular leak phenomenon. 

INABA, K. STEINMAN, R.M. (1984) Resting and sensitized T lymphocytes exhibit distinct (antigen presenting cell) requirements for growth and lymphokine release. Journal of Experimental Medicine, 160, 1717-1735. 

When tetramisole was administered four days after infection with the diabetogenic EMC-D virus, exacerbation of diabetes was usually seen. Since tetramisole causes release of lymphokines from activated T cells, these results suggest that EMC-D infection in animals developing diabetes also selectively activates Ts cells. The lymphokines released by activated Ts cells block the virus-specific antibody-producing B cells from receiving the helper signals from the Th cells. Consequently, antibody synthesis is blocked. 

In addition to effects mediated through glucocorticoid secretion (stress-related), a hypothetical mechanism for direct immunotoxicity of organophosphates is the inhibition of esterases and stabilization of the lysosomal membrane of lymphocytes, thus blocking release of lymphokines (Sharma and Reddy 1987). 

Inflammation is a non-specific reaction which can be induced by a variety of agents apart fiom microorganisms. Lymphokines and derivatives of arachidonic acid, including prostaglandins, leukotrienes and thromboxanes are probable mediators of the inflammatory response. The release of vasoactive amines such as histamine and serotonin (5-hydroxytryptamine) firm activated or damaged cells also contribute to inflammation. 

Immunoglobulins (Igs) can activate the complement system, which amplifies the immune response by enhancing chemotaxis, phagocytosis, and release of lymphokines by mononuclear cells that are then presented to T lymphocytes. The processed antigen is recognized by the major histocompatibility complex proteins on the lymphocyte surface, resulting in activation of T and B cells. 

Stimulation for 24 hours with LPS leads to the release of interleukin-1 [3, IL-6, IL-8, TNF-a and by prolonging the incubation period from 48 to 72 hours, the whole blood model can detect the release of other lymphokines [45], including IL-2, IL-4, IL-13 and IFN-y. Skewing of the T-helper cell response to antigens can likewise be detected by evaluating the pattern of cytokine release, corresponding to a predominance of Th 1 or Th2 cytokine production. The predictive value of these approaches is currently under investigation. 

Type 4, contact dermatitis. A cuta-neously applied drug is bound to the surface of T-lymphocytes directed specifically against it The lymphocytes release signal molecules (lymphokines) into their vicinity that activate macrophages and provoke an inflammatory reaction. 

T-lymphocytes are preferentially inhibited. The T-helper cell is the main target, although the T-suppressor cell also may be suppressed. Cyclosporine also inhibits lymphokine production and release including interleukin-2. 

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. 

Suppresses activation of T lymphocytes by inhibiting production and release of lymphokines, specifically interleukin-2... 

Lymphokines Chemicals released from activated lymphocytes that help mediate various aspects of the immune response. Common lymphokines include the interleukins and gamma interferon. 

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