Immunologic suppression

T-lymphocytes are the backbone of the immune system responsible for antigen presentation, cytotoxic effects, and cytokine release. Any attenuation of T-cell function can lead to widespread immunological suppression increas-... 

Lewisite, a vesicant with HD-Uke properties, causes a similar constellation of signs and symptoms involving the skin, eyes, and airways as well as systemic effects (e.g. increased capillary permeability) after absorption. However, it does not produce immunological suppression like mustard. Another difference is that the management of lewisite toxicity includes an antidote, British Anti-Lewisite (BAL) (Yue/u/.,2003). 

In an in vitro study involving human lymphocytes, it was demonstrated that ethanol and nicotine, at noninhibitory levels when added alone, showed significant suppression of natural killer cell activity when added combined. Natural killer cell activity is crucial to good health. The authors conclude that the immunological suppression effects of the ethanol/nico-tine mix may have clinical implicationsJ68l... 

In the future, tissue concentrations as well as blood concentrations may be measured. For example, while most centers currently measure cyclosporine concentrations to estimate the potential for immunosuppressive effects, it may be advantageous to monitor IL-2 concentrations. One of the primary actions of cyclosporine is the inhibition of IL-2 prodnction. Furthermore, perhaps it would be beneficial to measure tissue concentrations of IL-2 in the transplanted organ to get a better estimate of the extent of immunologic suppression. 

Ehnets, C.A. and Bowen, K.D., Immunological suppression in mice treated with hematoporphyrin derivative photoradiation. Cancer Res., 46, 1608,1986. 

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 antiepileptic drug phenytoin, an orally available class DB antiarrhythmic, is mainly effective in digitalis-induced arrhythmias. This diug exhibits nonlinear pharmacokinetics and a number of side effects including neuropathy, gingival hypetplasia, hepatitis, immunological disorders and suppression of white blood cells. 

Peters M, Waiting DM, Kelly K, Davis GL, Waggoner JG, Hoofnagle JH (1986) Immunologic effects of interferon-alpha in man treatment with human recombinant interferon-alpha suppresses in vitro immunoglobulin production in patients with chronic type B hepatitis. J Immunol 137 3147-3152... 

Walker CM, Levy JA (1989) A diffusible lymphokine produced by CD8+ T lymphocytes suppresses HIV replication. Immunology 66 628-630 Walker RE, Bechtel CM, Natarajan V, Baseler M, Hege KM, Metcalf JA, Stevens R, Hazen A, Blaese RM, Chen CC, Lehman SF, Palensky J, Wittes J, Davey RT, Falloon J, Polls MA, Ko-vacs JA, Broad DF, Levine BL, Roberts MR, Masur H, Lane HC (2000) Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. Blood 96 467 74... 

All the jellyfish venoms are toxic but also stimulate the cell mediated and humoral immunological systems of man. After injection of large doses of jellyfish venom into human skin, a perivascular mononuclear cell infiltration appears within the dermis. This infiltration is composed predominantly of helper inducer cells which produce suppressor activity. It appears that the NK enhancement of human leukocytes in patients envenomated by Chrysaora quinquecirrha is depressed when the clinical lesion is inflammatory (10). Recovery from this suppression follows the amelioration of the acute cutaneous reaction. In other instances, envenomated patients have abnormal macrophage migration tests (11). 

The success of antiretroviral therapy is measured by the degree to which the therapy (1) restores and preserves immunologic function, (2) maximally and durably suppresses HIV RNA, (3) improves quality of life, and (4) reduces HIV-related morbidity and mortality. The major outcome parameters are CD4+ lymphocyte absolute count and percentage, and plasma HIV RNA. Adequate immunologic response in antiretroviral-naive patients consists of an increase in CD4+ cell count that averages 100 to 150 cells/mm3 per year (with a faster response in the first 3 months), and a 1 log decrease in HIV RNA by 2 to 8 weeks after starting... 

Kim, G-Y, KimJ-H, AhnS-C et al. 2004. Lycopene suppresses the lipopolysaccharide-induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen-activated protein kinases and nuclear factor NF-kappa B. Immunology 113 203-211. 

This was the original hypothesis put forward by Lee (1970) and expanded by Ogilvie et al. (1973). Secretory products of N. brasiliensis do indeed decrease the amplitude of contractions of segments of uninfected rat intestine maintained in an organ bath, but a role for AChE in this phenomenon was discounted due to the heat stability of the parasite factor, and the inability to duplicate the effect with AChE from the electric eel (Foster et al., 1994). Subsequent investigations demonstrated that the suppression of contraction could be duplicated by a 30-50 kDa fraction of secreted products, which contained a protein of 30 kDa that was immunologically cross-reactive with mammalian vasoactive intestinal peptide (VIP). Moreover, an antibody to porcine VIP significantly reduced the inhibitory effect of parasite-secreted products on contraction in vitro (Foster and Lee, 1996). 

Dehlawi, M.S., Wakelin, D. and Behnke, J.M. (1987) Suppression of mucosal mastocytosis by infection with the intestinal nematode Nematospiroides dubius. Parasite Immunology 12, 561-566. 

Eklund, RK., Ghildyal, N., Austen, K.F. and Stevens, R.L. (1993) Induction by IL-9 and suppression by IL-3 and IL-4 of the levels of chromosome 14-derived transcripts that encode late expressed mouse mast cell proteases Journal of Immunology 151, 4266 273. 

Mansfield, L.S. and Urban, J.F. Jr (1996) The pathogenesis of necrotic proliferative colitis in swine is linked to whipworm induced suppression of mucosal immunity to resident bacteria. Veterinary Immunology and Immunopathology 50, 1-17. 

Some tumours secrete significant quantities of cytokines and additional regulatory molecules that can suppress local immunological activity. TGF-P (produced by many tumour types), for example, is capable of inhibiting lymphocyte and macrophage activity. 

Chowdhury, B.A. and R.K. Chandra. 1989. Effect of zinc administration on cadmium-induced suppression of natural killer cell activity in mice. Immunolog. Lett. 22 287-292. 

As noted above, the primary focus of immunotoxicology has been on suppression many of the early techniques grew out of basic immunology research, in which the function of various components of the immune response was determined by selective manipu-... 

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