Immunology

Several processes in the immune response are affected by lithium in vivo and in vitro 139). The proliferative responses of hamster lymphoid cells to concanavalin A or phytohemagglutinin, which stimulate mitosis in T cells, were enhanced by lithium in a serum-free culture system. Proliferative stimulation also was obtained with lithium using the B cell mitogen lipopolysaccharide, but the B cell mitogens dextran sulfate and trypsin had no effect 140-143). Lithium increased the effects of suboptimal concentrations of stimulants, but had smaller effects on stimulation by optimal concentrations. With concanavalin A, the response to optimal stimulatory concentrations was inhibited 140). Paradoxical results such as these may be due to inhibitory effects of lithium on adenylate cyclase, or to effects on membrane transport systems 141). Most of these experiments used very high concentrations of lithium, considerably in excess of normal therapeutic doses (maximal inhibitory concentrations were 10 mM with hamster cells and 5 mM with human lymphocytes). At therapeutic levels of lithium, increased incorporation of [ H]thymidine was seen in human peripheral blood mononuclear cells. 

The induction of primary antibody responses to sheep red blood cells is tested in a culture system containing T cells, B cells, macrophages, and antigen antibody secretion occurs after cell activation, proliferation, and differentiation. Lithium concentrations of 0.5 and 1.0 mM increased secretion of antibody by 153 and 177%, respectively. A concentration of 10 mM lithium reduced antibody production to 21% of the 

Parietal cell, thyroid, and antinuclear antibodies have been reported to be increased in lithium-treated patients (145-147). Autoantibodies directed at pituitary functions have also been demonstrated in lithium-treated patients and this may reflect modulation by lithium of pituitary and hypothalamic centers (148, 149). Tissue-specific autoantibodies such as these may or may not be related to autoimmune disease lithium may, in any case, modulate preexisting autoimmune processes rather than induce them (150). 

Leukocytosis occurs following lithium administration due to enhanced myelopoiesis and to alterations in the marginated pool of polymorphonuclear leucocytes (139, 151). Colony-stimulating factors from bone marrow macrophages are increased in the presence of lithium (152, 153). Maximum effects of lithium on myelopoiesis again were exhibited when conditions were suboptimal, when the numbers of colonies in the control cultures were low. This is of clinical importance because lithium may be used as an agent for limiting leukopenia in cancer chemotherapy (154). 

Lithium induces release of enzymes from human granuloc3de granules in vitro (155). Lithium also potentiates enz3one secretion by receptor-independent cytochalasin, but the secretory response to receptor-dependent chemotactic peptide f-MLP was not increased (156). Lithium in high concentrations (10 mM) induced release of lactoferrin from human granulocytes in vitro (157), but lithium effects on other aspects of granulocyte function are less clear and there are contradictory reports of its action (139, 158). 

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Ojcius D M, Niedergang F, Subtil A, Hellio R and Dautry-Varsat A 1996 Immunology and the confocal microscope Res. Immunol. 147 175-88... 

Sabri S, Richelme F, Pierres A, Benoliel A M and Bongrand P 1997 Interest of image processing in cell biology and immunology J. Immunol. Methods 208 1 -27... 

Species origin tests, used to determine whether the specimen is human or from another source, are immunological in nature. Host animals, usually rabbits, are injected with protein from another species. The animal creates antibodies to the unknown material. Semm from the host animal, containing species (human, bovine, equine, canine, etc) specific antibodies, is tested against a dilute solution of blood (antigens) collected as evidence. A positive reaction is determined by a visible band where the antibodies and antigens come into contact. 

R. E. Gaensslen, Sourcebook in Forensic Serology, Immunology andBiochemisty, National Institute of Justice, U.S. Department of Justice, U.S. Government Printing Office, Washington, D.C., 1983. 

W. D. Linscott, Einscott s Director of Immunological and Biological Reagents, 7th ed., Linscott s Directory, Santa Rosa, Calif., 1992—1993, 239 pp. 

Immunoassay is a method that identifies and quantifies unknown analytes usiag antibody—antigen reactions. Techniques are based ia immunochemistry, analytical chemistry, and biochemistry, with a history of development paralleling advances ia microbiology and immunology (see also Immunotherapeutic agents). 

EIA was originally developed as a histological technique to localize specific ceUular sites using the specificity of an immunological reaction (23). The resulting fluorescent antibodies can be detected in animal tissues at levels as low as 1 /tg/mL of body fluid. Eluorophore-labeled antibodies have also been used widely for flow cytometry appHcations using fluorescein antibodies to cell surface markers to detect and quantify specific cells (24). 

In the most common method for chemiluminescent immunoassay (GLIA), after the immunological reaction and any necessary separation steps, the labeled compounds or complexes react with an oxidizer, eg, hydrogen peroxide, and an enzyme, eg, peroxidase, or a chelating agent such as hemin or metal... 

Advances in immunology during the last part of the twentieth century have continued at a rapid rate and cytokines and immune cells having specific markers continue to be defined. A number of natural and synthetic immunotherapeutic agents have been discovered that can modulate components of the normal or aberrant immune system, through stimulation or suppression. However, most of these substances also have inherent adverse side effects. 

The number of known cytokines, as well as the diversity of biological functions, have led to a very complex and often confusing picture of the immunologic and nonimmunologic processes involved. The role of cytokiaes in local or systemic homeostatic mechanisms related to physiological functions may be utilized therapeutically for treatment of cancer and a variety of other diseases (2). Pharmaceutical research and development efforts surrounding lL-1 are typical examples of the cytokine inhibition approach to chronic inflammation research (2). 

Fig. 2. Structures of traditional antirlieumatic drugs having immunologic activity. See Table 2.

Table 2. Traditional Antirheumatic Drugs Having Immunological Activity ...

A new generation of antiinflammatory agents having immunosuppressive activity has been developed. The appearance of preclinical and clinical reports suggest that these are near entry to the pharmaceutical market. For example, tenidap (CP-66,248) (12) has been demonstrated to inhibit IL-1 production from human peripheral blood monocytes in culture (55). Clinically, IL-1 in synovial fluids of arthritic patients was reduced following treatment with tenidap. Patients with rheumatoid or osteoarthritis, when treated with tenidap, showed clinical improvement (57,58). In addition to its immunological effects, tenidap also has an antiinflammatory profile similar to the classical NSAIDs (59). Other synthetic inhibitors of IL-1 production are SKF 86002 (20) andE-5110 (21) (55). 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

R. Renoux and co-workers, in Th. Klein and co-workers. Biological Response Modifiers in Human Oncology and Immunology, Plenum... 

Luminol-based chemiluminescence methods have also been employed for detection of analytes in flowing stream analytical techniques such capillary electrophoresis (282), flow injection analyses, and hplc (267). AppHcations of the enhanced luminol methodology to replace radioassay methods have been developed for a number of immunological labeling techniques (121,283). 

W. R. Hanson, Prostaglandin Inhibitors in Tumor Immunology andimmunotherapj, CRC Press, Inc., Boca Raton, 1994, pp. 171—186. 

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