Interleukin antibodies

Take an Immuchip cartridge functionalised with the anti-interleukin antibodies (available at DiagnoSwiss), and plug it in the reception compartment of Immuspeed as shown in Fig. 50.1. 

Ah = Antibody IL = interleukin TNF =tumornecrosis factor INF = interferon LAK =lymphocyte-activated killer CSF =colony stimulating factors and FGF = fibroblast growth factor. 

This drug also is reported to activate macrophages, to iaduce polyclonal B-ceU activation as well as enhance specific antibody production m vivo, and to iaduce the synthesis of iaterferon and interleukin 1 (52). The iaduction of these important cytokiaes (and others) largely accounts for the profile of biological activity displayed by the pyrimidinones. Bropirimine is currentiy ia clinical evaluation for cancer, arthritis, and immunorestoration ia AIDS patients. 

Inhibition of inflammatory cytokines (Fig. 2) Humanized monoclonal anti-TNF antibodies (Infliximab (Remicade ), Adalimumab (Humira )) bind with high selectivity to human TNF-a and neutralize its activity. Thereby, infliximab decreases the effects of enhanced TNF levels during inflammatory disease such as production of proteases, chemokines, adhesion molecules, cyclooxygenase products (prostaglandins), and proinflammatory molecules such as interleukin-1 and -6. The antibodies may also recognize membrane-bound TNF-a on lymphocytes and other immune cells. These cells may subsequently become apoptotic or are eliminated via Fc-receptor-mediated phagocytosis. 

Immune Defense. Figure 3 Drugs involved in suppressing innate and adaptive immune response. Abbreviations mob monoclonal antibody, TCR T-cell antigen receptor, IL-2 interleukin-2, R receptor, CD cluster of differentiation. 

The chimeric human/murine (basiliximab and dacluzi-mab) or murine (inolimomab) monoclonal antibodies are specifically directed against a part (CD25) of the interleukin-2 (IL-2) receptor. Binding of one of these antibodies to CD25 thereby displaces physiological IL-2 and prevents proliferation of activated T-lymphocytes. 

Fever is the most common manifestation. The thermoregulatory centre in the hypothalamus regulates body temperature and this can be affected by endotoxins (heat-stable lipopolysaccharides) of Gram-negative bacteria and also by a monokine secreted by monocytes and macrophages called interleukin-1 (IL-1) which is also termed endogenous pyrogen. Antibody production and T-cell proliferation have been shown to be enhanced at elevated body temperatures and thus are beneficial effects of fever. 

These are supplied by the secretion of peptide molecules (termed cytokines or lymphokines) fiom a subset of the T-cell family (the helper T cells, TH cells). These peptide molecules (interleukins (IL) 2,4,5 and 6) stimulate the B cells to proliferate, undergo clonal expansion and mature into plasma cells which secrete antibody and also into the longer-hving, non-dividing memory cells. 

The inflammatory response in UC is propagated by atypical type 2 helper T cells that produce proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF).7 As discussed previously, a genetic predisposition to UC may partially explain the development of excessive colonic and rectal inflammation. The finding of positive perinuclear antineutrophil cytoplasmic antibodies (pANCA) in association with the human leukocyte antigen (HLA)-DR2 allele in a large percentage of patients with UC supports this theory.4,12... 

Sekido N, Mukaida N, Harada A, Nakanishi I, Watanabe I, Matsushima K. Prevention of lung perfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature 1993 365 654-657. 

Wada T, Tomosugi N, Naito T, et al. Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis. J Exp Med 1994 180 1135-1140. 

Pruijt JF, Fibbe WE, Laterveer L, et al. Prevention of interleukin-8-induced mobilization of hematopoietic progenitor cells in rhesus monkeys by inhibitory antibodies against the metalloproteinase gelatinase B (MMP-9). Proc Natl Acad Sci USA 1999 96(19) 10863-10868. 

Leckie MJ, ten Brinke A, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000 356(9248) 2144-2148. 

Low level activation of MPS Interleukin-I Amyloidosis Hyperplastic liver foci Altered stem cell kinetics Altered drug metabolism Altered response to drugs C Biotechnics For biotechnics (and specifically monoclonal antibodies), factors affecting safety include... 

Conrod, D.H., Ben-Sassort, S.Z., Le Gros, G., Finkelman, F.D. and Paul, W.E. (1990) Injection with anti-IgD antibodies markedly enhances Fc receptor mediated interleukin 4 production by non B, non T cells. Journal of Experimental Medicine 171,1497-1508. 

Korenaga, M., Hitoshi, Y., Takatsu, K. and Tada, I. (1994) Regulatory effect of anti-interleukin-5 monoclonal antibody on intestinal worm burden in a primary infection with Strongyloides venezuelensis. Journal of Parasitology 24, 951-957. 

Boirivant, M., Fuss, I.J., Chu, A. and Strober, W. (1998) Oxazolone colitis a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. Journal of Experimental Medicine 188, 1929-1939. 

Reported applications of SASD involve modification of lipopolysaccharide (LPS) molecules and studying their interaction with albumin and an antibody directed against LPS (Wollenweber and Morrison, 1985), identification of the murine interleukin-3 receptor and an N-formyl peptide receptor (Sorenson et al., 1986), crosslinking of factor V and Va to iodinated peptides... 

Duchmann R, Schmitt E, Knolle P, Meyer zum Buschenfelde KH, Neurath M Tolerance towards resident intestinal flora in mice is abrogated in experimental colitis and restored by treatment with interleukin-10 or antibodies to interleukin-12. Eur J Immunol 1996 26 934-938. 

Replacement of most Virtually all of the murine amino acid sequences with sequences found in human antibodies Fusion protein consisting of the diphtheria toxin linked to interleukin-2 (IL-2)... 

Monoclonal antibodies for in vivo use Cytokines (e.g. interferons and interleukins) Therapeutic enzymes Thrombolytic agents Hormones Growth factors Additional miscellaneous proteins Blood Blood proteins (e.g. albumin and blood factors) Vaccines Cell- and tissue-based products Gene therapy products Antitoxins, venoms and antivenins Allenergic extracts... 

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