Interleukin toxicity

Leonard, J.R et al., Effects of single-dose interleukin-12 exposure on interleukin-12-as-sociated toxicity and interferon-gamma production, Blood, 90, 2541, 1997. 

Huaux, F. et al., Lung Toxicity of Hard Metal Particles and Production of Interleukin-1, Tumor Necrosis Factor-a, Fibronectin, and Cystatin-c by Lung Phagocytes, Toxicol. Appl. Pharmacol., 132, 53, 1995. 

The effect of MAPK activation on cellular processes that affect cell function and the resulting pharmacology has been delineated using modem techniques such as knock-out cells and animals [1,3,6]. Activation of MAPK in inflammatory cells such as T-cells, B-cells, macrophages and eosinophils leads to expression and/or activation of pro-inflammatory genes and mediators such as interleukin-1(3 (IL-1(3), TNFa, IL-6, chemokines [e.g., IL-8, macrophage inflammatory factor-1 a, (3 (MIP-la,[3)J, MMPs and toxic molecules such as free radicals and nitric oxide [1,3]. These pro-inflammatory mediators induce cellular proliferation, differentiation, survival, apoptosis and tissue degradation/destruction and help induce chronic inflammation. Inhibition of any one or more of the MAPK family... 

Cytotoxins Cytokine, interleukin, growth factor or the receptor binding domains of these proteins Toxin, toxic protein or apoptosis-inducing protein IL-2-DAB TGFa-PE40 IL-2-BAX bFGF-SAP bFGF-RNase [123] [124,125] [126] [127] [128]... 

Concurrent administration of etanercept (another TNF -blocking agent) and anakinra (an interleukin-1 antagonist) has been associated with an increased risk of serious infections, and increased risk of neutropenia and no additional benefit compared with these medicinal products alone. Other TNF -blocking agents (including infliximab) used in combination with anakinra also may result in similar toxicities. 

Also when the cytokine interleukin 2 (IL-2) was used for cancer treatment, serious adverse effects were noted resulting in the so-called vascular leak syndrome (VLS) [98, 99]. VLS is a life-threatening toxicity marked by vasopermeability with hypotension induced during high dose IL-2 treatment of cancer patients [100]. VLS is caused by endothelial activation and can be induced in lungs and liver of mice by IL2 administration [99]. The mechanism of IL-2-induced VLS is still poorly understood and at present there is no specific therapy for VLS. For the investigation of these... 

The effect of echinacea on the immune system is controversial. In vivo human studies using commercially marketed formulations of E purpurea have shown increased phagocytosis, total circulating white blood cells, monocytes, neutrophils, and natural killer cells but not immunostimulation. In vitro, Epurpurea juice increased production of interleukins-1, -6, and -10, and tumor necrosis factor- by human macrophages. Enhanced natural killer cell activity and antibody-dependent cellular toxicity was also observed with E purpurea extract in cell lines from both healthy and immunocompromised patients. Studies using the isolated purified polysaccharides from Epurpurea have also shown cytokine activation. Polysaccharides by themselves, however, are unlikely to accurately reproduce the activity of the entire extract. 

Interleukin-2 (T-cell growth factor Fig. 30-6A) is secreted by some activated T-lymphocytes. This 133-residue largely helical protein is involved in generation of cytotoxic T-cells, stimulation of interferon release, and of release of a B-cell growth factor.269 Considerable excitement has accompanied the possibility of activating lymphocytes with IL-2 produced from cloned genes in bacteria to increase their ability to kill cancer cells. However, IL-2 is toxic, and this is limiting its use. See also Chapter 31, Section C. 

Lotz MT, Matory YL, Rayner AA. 1986. Clinical effects and toxicity of interleukin-2 in patients with cancer. Cancer. 58 2764—2772. 

Vial T, Descotes J. Clinical toxicity of interleukin-2. Drug Saf 1992 7(6) 417-33. 

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