Interleukin prediction

Because of the multiple degradation pathways that may take place at elevated temperature, protein stability monitoring data may not conform to the Arrhenius relationship, and the maximum temperature selected for accelerated stability studies must be carefully selected. Gu et al. [32] described the different mechanisms of inactivation of interleukin-1 (3 (IL-1 (3) in solution above and below 39°C. In this example, the multiple mechanisms precluded the prediction of formulation shelf life from accelerated temperature data. In contrast, by working at 40° C and lower, Perlman and Nguyen [33] were able to successfully extrapolate data from stability studies of tissue plasminogen activator down to 5°C. 

In this new scenario much attention is being paid to the investigation of a series of markers of inflammation as reliable indicators of coronary risk. Their value is stressed by the observation that up to one third of events occurs in subjects without traditional risk factors. The C-reactive protein (CRP) seems to provide the strongest risk prediction for CHD in women (Albert 2000 Ridker 2001), although homocysteine, interleukin-6 (IL-6), and lipoprotein (a) [ Lp (a) ], among others, have each been independently associated with increased risk for CHD in women (for a review see Davison and Davis 2003 Rader 2000). 

Stimulation for 24 hours with LPS leads to the release of interleukin-1 [3, IL-6, IL-8, TNF-a and by prolonging the incubation period from 48 to 72 hours, the whole blood model can detect the release of other lymphokines [45], including IL-2, IL-4, IL-13 and IFN-y. Skewing of the T-helper cell response to antigens can likewise be detected by evaluating the pattern of cytokine release, corresponding to a predominance of Th 1 or Th2 cytokine production. The predictive value of these approaches is currently under investigation. 

Kaempfer, R. et al., Prediction of response to treatment in superficial bladder carcinoma through pattern of interleukin-2 gene expression, J Clin. Oncol., 14, 1778, 1996. 

Reid I, Sharpe I, McDevitt J, Maxwell W, Emmons R, Tanner WA, Monson JR. Thyroid dysfunction can predict response to immunotherapy with interleukin-2 and inter-feron-2 alpha. Br J Cancer 1991 64(5) 915-8. 

The predicted amino acid sequence of the clone obtained from NG108-15 cells (Fig. 1) identified the delta opioid receptor as a member of the seven-transmembrane family of G protein-coupled receptors. The receptor had seven hydrophobic, predicted transmembrane domains (TMDs) and close homology to many other G protein-coupled receptors, including receptors for somatostatin, interleukin-8 and angiotensin. This structural homology confirmed the widely held notion that opioid receptors would indeed be members of this enormous family of receptors (the human genome has recently been calculated to contain approximately 950 G protein-coupled receptors [29]). 

In Table 32.6 the predicted parameter estimates derived from the allometric equations in Table 32.5 are compared with the corresponding parameter estimates reported in humans. The observed values of Pi for the macromolecules listed fall within the expected range of observed results. However the observed clearances of Factor IX (FIX) and interleukin-12 (IL-12) were not predicted from allometry. Factors such as species specificity in the endothelial binding of FIX (22) or saturation of clearance mechanisms may account for the inability to predict these parameters in humans. 

E. Tarkowski, L. Rosengren, C. Blomstrand, C. Wikkelso, C. Jensen, S. Ekholm, and A. Tarkowski. Early Intrathecal Production of Interleukin-6 Predicts the Size of Brain Lesion in Stroke. Stroke, 26 (1995) 1.393-1.398. 

Tarkowski E, Rosengren L, Blomstrand C, Wikkelso C, Jensen C, Ekholm S, Tarkowski A (1995) Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke 26 1393-1398. 

Thermal techniques such as isothermal calorimetry (ITC) and differential scanning calorimetry (DSC) have been used in formulation screens to predict the formulation with the greatest stability based on the assumption that excipients that increase the of the protein will stabilize the molecule at the recommended storage temperature. For example, a screen of preservatives performed during formulation development for interleukin-1 receptor found that the for the formulation... 

Citterio G, Fragasso G, Rossetti E, Di Lucca G, Bucci E, Foppoli M, Guerrieri R, Matteucci P, Polastri D, Scaglietti U, Tresoldi M, Chierchia SL, Rugarli C. Isolated left ventricular filling abnormahties may predict interleukin-2-induced cardiovascular toxicity. J Immunother Emphasis Tumor Immunol 1996 19(2) 134-41. 

The cause of preterm labor is unknown, but recent evidence in a mouse model indicates that a maternal serum surfactant protein, SP-A, may trigger labor. Fetal fibronectin and cervical ultrasound have proven value for evaluating patients suspected of having preterm labor. The fetal fibronectin test is described later in the section entitled Laboratory Tests. Use of salivary estriol, corticotropin-releasing hormone, and interleukin-6 for preterm labor prediction is being investigated. 

Goepfert AR, Goidenberg RL, Andrews WW, Hauth JC, Mercer B, lams J, et al. The preterm prediction study association between cervical interleukin 6 concentration and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 2001 184 483-8. 

Also, the inclusion of EF and different biomarkers added significant prognostic information over TIMI and PREDICT scores. Recently, other markers, such as CRP, and different interleukins have been added to the risk assessment (Anguera et al, 2002 Zairis et al, 2002), as well as BNP (Bassan et al, 2005) and PAPP (Heeschen et al, 2004). Even the value of multiple biomarkers added to the value of quantitative ST-segment depression has been recently published (Westerhout et al, 2006). 

Jancic I, Arsenovic-Ranin N, Sefik-Bukilica M, Zivojinovic S, Damjanov N, Spasovski V et al (2013) 174G/C interleukin-6 gene promoter polymorphism predicts therapeutic response to etanercept in rheumatoid arthritis. Rheumatol Int 33 1481-1486... 

There are not many examples of cytokines that have been approved as therapeutic agents. In part, this lack is due to the pleiotropic effects of these agents (74), which makes the overall effect difficult to predict, and because administration of these agents will often mediate increased immunological response. In general, the administration of interleukins results in elevated blood cell counts, particularly white cells. However, because they help to increase blood cells and also induce... 

Aureli, L., Cruciani, G., Cesta, M.C., Anacardio, R., De Simone, L. and Moriconi, A. (2005) Predicting human serum albumin affinity of interleukin-8... 

R. T. Kroemer, S. W. Doughty, A. J. Robinson, W. G. Richards. Prediction of the three-dimensional structure of human interleukin-7 by homology modeling. Protein Eng. 

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