Interleukin early studies

In addition to being able to recognize the different cells involved in the acquired immune system of marine mammals, it is important to assure that the cells perform their functions appropriately. The ability of lymphocytes to proliferate upon stimulation (usually with mitogens) has been studied for several decades [1,12,14,15, 32-35], Recent advances include the demonstration of a conserved specificity for standard mitogens used in beluga whales [32] and harbor seals [33], An assay to assess the expression of the receptor for interleukin-2 (IL-2), an early event in lymphocyte activation, was adapted in harbor seals [35], bottlenose dolphins [36], and sea otters [37], Molecular and biochemical mechanisms of activation of beluga T lymphocytes do not vary substantially from those in other mammals [38],... 

This is not to say that cardiotoxicity is not seen with biopharmaceuticals. Cardiomyopathy is now a well-recognized complication of trastuzumab and and has been reported with bevacizumab treatment, in particular in combination with other cytotoxic cancer therapies [20]. Myocarditis and pericarditis are a well-documented complications of vaccinia immunization [21], and could also complicate use of a pox-virus vector for other therapeutics. In 1995 Genetics Institute suspended phase 2 cancer trials of Interleukin-12 for serious tox-icities including cardiac arrhythmia. However, such toxicities are best detected by incorporation of biomarkers for myocardial damage such as troponin-T into preclinical and early clinical studies, and continual ECG monitoring for arrhythmia in preclinical and early clinical studies, not by in vitro explorations of electrophysiology. 

Interleukin-12, an immunomodulatory cytokine, has potential effects in several cancer and infectious diseases. Although interleukin-12 was considered to be reasonably safe in early clinical trials, severe and sometimes fatal multiple organ adverse effects have been described in subsequent studies (SEDA-20, 336). This unexpected profile of toxicity was later shown to result from schedule-dependent toxicity, which occurred only in patients with cancer who received multiple high doses without an initial single dose of interleukin-12 (1). This severe toxicity has since been avoided. 

Very few studies have examined the role of cytokines and chemokines in acetaminophen toxicity in the clinical setting. Interleukin 8 (the human homologue of MIP-2) was shown to be increased in patients with acetaminophen toxicity and to correspond with markers of hepatic injury (James et al. 2001). Further investigation in this area may help to identify potential early determinants of severe cases of acetaminophen toxicity. 

Studies have shown that niacin significantly reduces ICAM-1, VCAM-1, PECAM and E-selectin levels. It also reduced the tumour necrosis (actor-alpha (TNF-a) induced rise in ICAM (it does this by reducing mRNA-induced expression of ICAM). It also decreased the production of ICAM through its reduction in interferon-y (IFN-y) and interleukin-1 (IL-l). Through these mechanisms, niacin induces a reduction of monocyte adhesion in endothelial cells This may possibly lead to decreased leucocyte adhesion to endothelium, which is an important early event in atherosclerosis (Tavintharan et al. 2009). 

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