Cytokine serum level during severe sepsis in human IL-6 as a marker of severity.

Forty critically ill surgical patients with documented infections were studied during their stay in an intensive care unit. Among these patients, 19 developed septic shock and 16 died, 9 of them from septic shock. Interleukin 1 beta (IL-1 beta), tumor necrosis factor (TNF alpha), and interleukin 6 (IL-6) were measured each day and every 1 or 2 hours when septic shock occurred. Although IL-1 beta was never found, TNF alpha was most often observed in the serum at a level under 100 pg/mL except during septic shock. During these acute episodes TNF alpha level reached several hundred pg/mL, but only for a few hours. In contrast, IL-6 was always increased in the serum of acutely ill patients (peak to 500,000 pg/mL). There was a direct correlation between IL-6 peak serum level and TNF alpha peak serum level during septic shock and between IL-6 serum level and temperature or C-reactive protein serum level. Moreover, IL-6 correlated well with APACHE II score, and the mortality rate increased significantly in the group of patients who presented with IL-6 serum level above 1000 pg/mL. Thus, IL-6 appears to be a good marker of severity during bacterial infection. [1]

Serum Level of Interleukin 6 as a Prognosis Factor in Metastatic Renal Cell Carcinoma

Interleukin (IL) 6 was measured in the serum of 138 patients with metastatic renal carcinoma before the initiation of IL-2 treatment. IL-6 was detectable in 66 patients with renal cancer (48%) and in only 8 of 70 normal adults (11%). Serum C reactive protein (CRP) and IL-6 levels are correlated, suggesting that IL-6 is involved in CRP increase in these patients. The interval between diagnosis of the primary tumor and metastasis was shorter in patients with a detectable serum IL-6 and/or serum CRP level >50 mg/liter. Serum IL-6 and CRP levels were higher in subgroups of patients previously defined as having a poor life expectancy according to the Eastern Cooperative Oncology Group criteria.

Pretreatment concentrations of IL-6 and CRP were higher in patients who experienced progressive disease after IL-2 treatment. Patients with detectable IL-6 had a shorter survival from the beginning of IL-2 treatment than patients without circulating IL-6 (median, 8 versus 16 months). Similarly, the median survival from the beginning of IL-2 therapy of patients with CRP levels >50 mg/liter was 6 months, compared to 16 months in those with CRP levels below this threshold. None of the 21 patients with serum IL-6 concentrations >300 pg/ml achieved response to any of the three IL-2 regimens. This subgroup has a median survival of 5 months after IL-2 treatment and consisted of 15% of the patients in our series. These results indicate that serum IL-6 and CRP levels are adverse prognosis factors in patients with metastatic renal cell carcinoma. Serum IL-6 level could help in the selection or stratification of the patients in future IL-2 trials. [2]

Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein.

Mannan-binding protein (MBP) is a serum lectin participating in the innate immune defense by opsonizing various microorganisms for phagocytosis. Opsonization defect due to MBP deficiency and low levels of the protein can partially be explained by the dominant effect of three different mutations in the structural part of the MBP gene. Large interracial differences in the frequencies of these variants have previously been described, but they cannot explain the large interindividual variation in MBP serum concentration. We describe the existence of additional polymorphisms at positions -550 (H/L variants) and -221 (X/Y variants) in the promoter region of the gene. The promoter haplotypes, HY, LY, and LX, show associations with high, medium, and low levels of MBP serum concentrations, respectively. Moreover, this represents a genetic system with additive effect of haplotypes in which a low producing LX haplotype in the homozygous state down-regulates the basal expression of MBP as effectively as a single structural variant. Populations of pure Eskimos, Caucasoids, and black Africans show marked interethnic differences in the frequencies of promoter haplotypes regulating the expression of the normal peptide, with the HY haplotype frequency varying from 0.83 in Eskimos via 0.33 in Caucasoids to 0.08 in Africans. The LY haplotype frequency varies from 0.04 in Eskimos via 0.39 in Caucasoids to 0.23 in Africans. The LX haplotype frequency varies from 0.03 in Eskimos via 0.24 in Caucasoids to 0.23 in Africans. The effect of the promoter variants can explain almost all of the ethnic differences not explainable by the structural variants alone. [3]

Correlation of Serum IL-17 with Level of Vitamin D and IgE in Asthmatic Patients

Background: Allergic asthma is a chronic inflammatory disorder of the airways caused by   hypersensitivity and  characterized by Th2 cytokine i.e. IL-4, that contribute to enhanced proliferation and differentiation of Th2 cells and switch of B cells from IgM to IgE production. Vitamin D also has a role in proliferation, differentiation, apoptosis of cells of the immune system, production of cytokines, and immunoglobulins. Elevated levels of IL-17 have been documented in bronchial submucosa and relationship of IL-17 and severe hyper responsiveness of airways have been established. Therefore, a study was conducted to determine serum level of vitamin D, IgE and IL-17 in patients of bronchial asthma.

Methodology: It was a comparative study, which included 82 subjects i.e. Group-I (41 subjects without asthma), and group-II (41 asthmatic patients). Serum levels of IL-17, IgE and vitamin D were determined by ELISA technique and the results were analyzed by using SPSS-20.0. Mann-Whitney-U, Chi-square and Pearson’s correlation tests were used for data analysis.

Results: Mean ± SD of total serum IgE level of bronchial asthma patients was high (861.6±559.2 IU/ml) compared to controls (204.7±237 IU/ml) and on comparison there was statistically significant difference (p value 0.000). Mean ± SD of serum vitamin D level in asthmatics was 28.04±17.67 ng/ml while in non-asthmatics it was 27.27±17.01 ng/ml and on comparison the difference was not statistical significant (p=0.915). Mean ± SD of serum level of IL-17 was high in asthmatics (920.08±732 pg/ml) as compared to non-asthmatics (767.71±811 pg/ml) and on comparison the difference was not statistically significant (p=0.108). In asthmatics, there was positive correlation of serum level of vitamin D and IL-17 (r=0.101) and there was an association (p=0.001) of family history with asthma.

Conclusion: Asthmatics had raised serum level of IgE, vitamin D and IL-17 as compared to controls and on comparison only the difference of IgE was statistically significant. Further, an association of family history of asthma was observed in asthmatic patients. [4]

Vitamin D3 Serum Level Relationship with Severity and Activity of Lupus Disease

Background: The importance of vitamin D and its inhibitory effects has been proven in many autoimmune diseases. The present study was conducted to determine the relationship between serum levels of vitamin D3 and the severity and activity of lupus disease.

Materials and Methods: In a descriptive-analytical study, serum levels of vitamin D3 were measured in 100 patients with lupus and 100 non-infected individuals as a control group with matching age and sex. The deficiency and insufficient level of vitamin D was calculated based on 10 and 30 ng/mL, respectively. The medical history of all patients was checked out, and the disease activity was evaluated based on SLEDAI criteria. Finally, the collected data were analysed by SPSS software.

Result: In the present study 96 women and 4 men with lupus participated. The mean level of vitamin D3 in the lupus patients group was significantly higher than the control group (42.44 ± 16.87 ng/mL vs. 81.69 ± 13.30 ng/mL; p=0.012). Also, 79% of patients with lupus and 87% of patients in the control group had deficiency and insufficient vitamin D levels. There was no significant relationship between vitamin D3 level and severity of disease (SLEDAI) (P = 0.362). But there was a significant relationship between the duration of the disease and serum levels of vitamin D3 (P = 0.045).

Conclusion: Given that vitamin D deficiency in the control group and SLE patients are of        common difficulties, but vitamin D levels in patients with SLE did not correlate with the disease activity. [5]

Reference

[1] Damas, P., Ledoux, D.I.D.I.E.R., Nys, M., Vrindts, Y.V.O.N.N.E., De Groote, D.O.N.A.T., Franchimont, P. and Lamy, M., 1992. Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Annals of surgery, 215(4), p.356.

[2] Blay, J.Y., Negrier, S., Combaret, V., Attali, S., Goillot, E., Merrouche, Y., Mercatello, A., Ravault, A., Tourani, J.M., Moskovtchenko, J.F. and Philip, T., 1992. Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma. Cancer Research, 52(12), pp.3317-3322.

[3] Madsen, H.O., Garred, P., Thiel, S., Kurtzhals, J.A., Lamm, L.U., Ryder, L.P. and Svejgaard, A., 1995. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. The Journal of Immunology, 155(6), pp.3013-3020.

[4] Naz, F., Afzal, N., Shahzad, F., Kashif, M., Javed, K., Jahan, S. and Latif, W. (2016) “Correlation of Serum IL-17 with Level of Vitamin D and IgE in Asthmatic Patients”, Journal of Pharmaceutical Research International, 11(1), pp. 1-8. doi: 10.9734/BJPR/2016/23474.

[5] Rajaei, E., Mola, K., Dargahi-Malamir, M. and Hatami, S. (2018) “Vitamin D3 Serum Level Relationship with Severity and Activity of Lupus Disease”, Journal of Pharmaceutical Research International, 23(6), pp. 1-7. doi: 10.9734/JPRI/2018/42473.