|Year : 2020 | Volume
| Issue : 3 | Page : 166-171
Changes in metabolic parameters in psoriasis patients treated with interleukin-12/23 blockade (ustekinumab)
Chau Yee Ng1, Yu-Huei Huang2, I-Shiang Tzeng3, Su-Hsun Liu4, Ya-Ching Chang2
1 Department of Dermatology, College of Medicine, Chang Gung Memorial Hospital, Linkou Branch; School of Medicine, College of Medicine; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
2 Department of Dermatology, College of Medicine, Chang Gung Memorial Hospital, Linkou Branch; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
3 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University; Department of Statistics, National Taipei University, Taipei, Taiwan
4 School of Medicine, College of Medicine, Chang Gung University; Department of Family Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
|Date of Submission||03-Mar-2020|
|Date of Decision||10-May-2020|
|Date of Acceptance||27-May-2020|
|Date of Web Publication||10-Sep-2020|
Dr. Ya-Ching Chang
Department of Dermatology, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fushin Street, Taoyuan
Source of Support: None, Conflict of Interest: None
Background: The associations between psoriasis, metabolic syndrome, and cardiovascular events are increasingly recognized. Studies have shown decreased cardiovascular events with the treatment of methotrexate and anti-tumor necrosis factor-α. However, effects of interleukin (IL)-12/23 blockade remain debatable. Objectives: Our study sought to investigate the effect of IL-12/23 blockade on the metabolic parameters in patients with psoriasis. Methods: We performed a retrospective cohort study to assess 93 consecutive patients with moderate-to-severe plaque-type psoriasis who received IL-12/23 blockade (ustekinumab) for 24 weeks between January 2012 and May 2016. Results: Metabolic parameters and disease activity (psoriasis area severity index score) at baseline and 24 weeks of treatment were collected. At week 24 (wk24), the disease activity improved significantly (mean: baseline, wk0: 21.35 ± 11.55 to wk24: 6.87 ± 6.81, P < 0.0001), with a significant reduction of erythrocyte sedimentation rate. Conversely, body mass index was significantly elevated in PASI-75 responders at wk24 of treatment and was independent of disease severity. Fasting sugar and triglyceride level were elevated at wk24. Cholesterol (Chol), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) remained unchanged. These metabolic parameters were not correlated with the improvement in disease severity after ustekinumab treatment. Nonetheless, the atherogenic index, LDL/HDL ratio, and Chol/HDL ratio remained unchanged. Male gender is a predictor of elevated plasma triglyceride level. Conclusion: Our results suggest that despite tremendous improvement in disease activity after ustekinumab treatment, obesity, fasting sugar, and hypertriglyceridemia are still present in these patients. Regular screening of lipid profile and obesity control is advised during the treatment of ustekinumab, especially in male psoriasis patients with predisposing cardiovascular risks.
Keywords: Metabolic parameters, psoriasis, ustekinumab
|How to cite this article:|
Ng CY, Huang YH, Tzeng IS, Liu SH, Chang YC. Changes in metabolic parameters in psoriasis patients treated with interleukin-12/23 blockade (ustekinumab). Dermatol Sin 2020;38:166-71
|How to cite this URL:|
Ng CY, Huang YH, Tzeng IS, Liu SH, Chang YC. Changes in metabolic parameters in psoriasis patients treated with interleukin-12/23 blockade (ustekinumab). Dermatol Sin [serial online] 2020 [cited 2020 Oct 23];38:166-71. Available from: https://www.dermsinica.org/text.asp?2020/38/3/166/294709
| Introduction|| |
Psoriasis is a chronic inflammatory skin disorder that affects approximately 1%–3% of the general population., Patients with psoriasis vulgaris are known to have an increased mortality rates compared to the general population, and cardiovascular event is among the most important cause of death in patients with severe psoriasis.,,, An increased risk of obesity and metabolic syndrome was found in psoriasis, and these were established risk factors for cardiovascular events., Severe psoriasis is correlated with metabolic syndrome. Studies suggested that chronic systemic inflammation plays a key role in metabolic disorders and psoriasis., Psoriasis and atherosclerosis both share a common upregulation of Th1 and Th17 cytokine, systemic expression of adhesion molecules, and endothelins. Through improvement in the disease activity, one would expect an improvement in the lipid profiles, atherosclerosis, and cardiovascular events. Disease activity suppression with methotrexate and antitumor necrosis factor was associated with reduced cardiovascular risk. Interestingly, previous reports have shown an increased total cholesterol (Chol) and triglyceride following treatment of anti-tumor necrosis factor (TNF) therapy without affecting the atherogenic index.,, To date, reports of anti-interleukin (IL)-12/23 to metabolic parameters and cardiovascular risk are still limited and were rather controversial. Since obesity and dyslipidemia were reversible risk factors for cardiovascular events, our aim of this study was to ascertain the effects of IL-12/23 blockade on metabolic parameters and obesity by the disease activity and treatment responses in patients with psoriasis.
| Materials and Methods|| |
A retrospective cohort study was carried out in a Chang Gung Memorial Hospital, Linkou, from January 2012 to May 2016. The study population comprised consecutive patients older than ≥18 years of age with the diagnosis of chronic plaque-type psoriasis vulgaris made by a certified dermatologist. All patients received three doses of IL-12/23 antagonist (ustekinumab) injection (45 mg subcutaneously [SC] for patients weighing <100 kg and 90 mg SC for patients weighing >100 kg) at week 0 (wk0), week 4, and week 16 of a treatment course. This study was approved by the Institutional Review Board of the Ethical Standards Committee of Chang Gung Memorial Hospital (approval no. 201600056B0) before study initiation and was conducted in accordance with the Declaration of Helsinki and all relevant local laws, regulations, and guidelines for the use of human subjects. Patient informed consent was not required by the Ethical Standards Committee due to retrospective nature.
Disease activity (Psoriasis Area Severity Index (PASI)) and body mass index (BMI) were assessed at baseline (wk0) and week 24 (wk24). Assessments of acute phase reactants (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), fasting glucose, serum lipoprotein concentration including total Chol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride at wk0 and wk24 were collected. Lipid protein ratios reflecting cardiovascular risks (atherogenic index of plasma [AIP], Chol/HDL ratio, and LDL/HDL ratio) were calculated. The changes of metabolic parameters in correlation to disease activity (PASI score, ESR, and CRP) at wk0 and wk24 of IL12/23 blockade (ustekinumab) treatment were assessed. Subsequently, we compared the differences of metabolic parameters and lipoprotein ratios in the PASI-75 responders (PASI score with more than 75% improvement [PASI-75+]) versus non-PASI-75 responders (PASI score with <75% improvements [PASI-75−]).
Results were expressed as mean ± standard deviation (SD) for normally distributed data and median (interquartile range [IQR]) for nonnormally distributed data. Descriptive statistics and comparative analysis were performed using the (SAS Institute Inc., Cary, NC, USA). Categorical variables were assessed using the Chi-squared test. Quantitative variables were analyzed using a t-test and paired t-test (for BMI). Wilcoxon signed-rank test was used to analyze the metabolic parameters of the patients before and after treatment. Multiple linear regression was later used for possible predictors of triglyceride increase after treatment found in the initial analyses. McNemar test was used to analyze the changes of lipoprotein ratios. The level of significance for all two-tailed analysis was at 0.05.
| Results|| |
A roster of 93 consecutive patients with moderate-to-severe plaque-type psoriasis were included in this study. All patients had initially a high disease activity (PASI score >10) that justified the use of ustekinumab. The demographic characteristics of these patients at baseline including age, BMI, gender, pre/postmenopause, smoking, alcoholism, disease duration, and underlying comorbidities were described in [Table 1]. The mean age at treatment was 41.86 ± 10.56 years old, with an average disease duration of 15.21 ± 8.4 years. Males (71%) were slightly more than females (29%) (P = 0.77). The baseline age, disease duration, gender, comorbidities, and BMI were similar in both PASI-75 + and PASI-75− (P > 0.05). All patients tolerated ustekinumab infusions throughout the study with no adverse reactions. No significant changes in smoking/alcohol habit or dosage of background medications were registered during the study period.
|Table 1: Demographic and clinical characteristics of 93 psoriasis patients receiving IL12/23 blockade (ustekinumab/ Stelara®)|
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PASI score improved significantly over the study period from a wk0 mean of 21.35 ± 11.55–6.87 ± 6.81 at wk24 (P< 0.0001). ESR improved after treatment. Interestingly, BMI significantly elevated after treatment (mean [±SD]: w0: 26.95 [1.404] and wk24: 27.59 [±1.67], P < 0.0001). Uric acid was lower at wk24 compared to baseline (median wk0: 6.8 [IQR: 6.98, 8.3] and wk24: 6.7 [5.6, 7.7], P = 0.132). Fasting sugar and triglyceride both increased significantly after ustekinumab treatment (fasting sugar, median [IQR], wk0: 91.5 (85, 102) and wk24: 93 (88, 105), P < 0.0431; triglyceride, w0: 122.5 (86, 150.5) and wk24: 129 (96, 173), P < 0.0021). We further compared changes in disease activity, inflammatory markers, and metabolic parameters between PASI-75+ and PASI-75− groups, as shown in [Table 2]. Our results demonstrate that PASI and ESR were significantly improved in both the groups. BMI was significantly elevated at wk24 compared to wk0 in PASI-75+ (mean [±SD], wk0: 25.64 [±5.27] and wk24: 26.55 [±5.55], P < 0.0001) but not in PASI-75− patients. Triglyceride level was significantly elevated in both the groups. Nevertheless, the lipoprotein ratios including AIP, LDL/HDL ratio, and Chol/HDL ratio of both risk categories remained unchanged [Supplementary Table 1]. Subsequently, we performed a multiple linear regression to investigate the predictors of serum triglyceride level elevation in these patients, as shown in [Table 3]. Our results show that male gender alone is significantly correlated with the elevation of triglyceride level, whereas BMI, PASI-75 response, alcohol, and the presence of comorbidities were not.
|Table 2: Changes of inflammatory markers and metabolic parameters between after receiving IL12/23 blockade (ustekinumab/Stelara®)|
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|Table 3: Predictors of serum triglyceride level difference at week 0 and week 24 of treatment with IL12/23 blockade (ustekinumab/Stelara®) in patients with psoriasis|
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| Discussion|| |
Psoriasis is a chronic inflammatory disease that is more than skin deep. Associations between psoriasis and metabolic comorbidities such as obesity, hyperlipidemia, diabetes, and cardiovascular events have been well demonstrated.,,,,, “Psoriatic march” was proposed by Boehncke et al. to describe the evolution of metabolic syndrome to cardiovascular events in psoriatic disease. The key mediators to the pathogenesis of psoriasis, obesity, metabolic syndrome, and cardiovascular events all lie in chronic Th-1 inflammation. Through controlling psoriasis disease activity, one would expect to provide beneficial effects on these metabolic parameters and eventually lower the risk of cardiovascular events. However, only methotrexate and antitumor necrosis factor were found to reduced cardiovascular risk in psoriasis patients, whereas the effect of IL-12/23 antagonist to cardiovascular event remains debatable.,, Tzellos et al. systemically analyzed the major adverse cardiovascular events (MACEs) in patients with psoriasis after treatment of ustekinumab or briakinumab and found that the MACEs events increase in both treatment groups. The study was, however, contradictory to a previous study by Ryan et al. which showed no increased risk of MACEs in the treatment arm of anti-IL12/23 antibodies. The discrepancy in both studies was caused by different Peto's meta-analysis methods and risk-difference methods, respectively. Lipid profile and BMI are metabolic parameters that are strong, yet reversible predictors of MACEs. Studies have shown that antitumor necrosis factor improved insulin sensitivity and alters lipid profile in psoriasis patients. To our knowledge, there was no previous report regarding the effect of IL-12/23 antagonist (ustekinumab) on lipid profile and studies on the impact of BMI and correlation to disease severity were limited.,
In this study, a significant improvement in disease activity was found at w24 of ustekinumab treatment. Interestingly, BMI, fasting sugar, and triglyceride were significantly elevated at w24 of treatment. The elevation of BMI and triglyceride was more prominent in the PASI-75+ patients. On subsequent multiple linear regression analysis, we found that serum triglyceride elevation was correlated to male gender. Nevertheless, the lipoprotein ratios including Chol/HDL ratio, LDL/HDL ratio, and AIP, which are good predictors for cardiovascular risks, did not change significantly during treatment period.
Hypertriglyceridemia is a known independent risk factor of cardiovascular disease. We observed a significant correlation between fasting triglyceride and male gender but not with other variables. The baseline triglyceride level of psoriasis patients who are smokers was not higher than of nonsmoker. However, after treatment, the level of triglyceride in psoriasis patients who are nonsmokers increased more than of psoriasis patients who are smokers. Previous studies have shown that cigarette smoking is associated with increased serum triglyceride that portends a higher risk for coronary artery diseases and secondary insulin resistance. Studies have shown that smoking causes changes in the expression of triglyceride-rich lipoprotein causing hypercoagulability and reduced fibrinolysis., Conversely, an increased prevalence of smoking in psoriasis patients and an increased incidence of psoriasis among smokers have been reported, resulting in a vicious cycle. Interestingly, a similar effect has not been observed in psoriasis patients who are nonsmokers. One possible explanation is that other contributing factors of triglyceridemia may exceed the effect of smoking. In this study, we have found that male psoriasis patients are more prone to triglyceride elevation. Studies have shown that only men but not women with hypertriglyceridemia are significantly associated with arterial stiffness that determines coronary artery disease; hence, we should closely monitor and treat these patients to prevent this notorious sequela.
Although yet fully understood, the relationship of pro-inflammatory cytokines in psoriasis and metabolic parameters has been studied., In psoriasis skin, IL-12 and IL-23 induce the differentiation of naive CD4+ T-cells into highly pathogenic helper T-cells Th1 and Th17, respectively., These helper T-cells produce inflammatory cytokines such as tumor TNF-α, IL-17, IL-6, and IL-22., These pro-inflammatory cytokines that are heavily involved in the pathogenesis of psoriasis also play an important role in metabolic regulations. For instance, TNF-α is involved in insulin regulation and lipid metabolism and is overexpressed in obese patients., Furthermore, low levels of IL-10 in psoriasis patients were linked to metabolic syndrome, weight gain, and insulin resistance., One would expect an antagonist to these pro-inflammatory cytokines to have an opposite effect, however, studies have reported increased levels of triglycerides in mice treated with anti-TNF-α., Significant weight gain and increased BMI were also reported after anti-TNF-alpha treatment. Furthermore, IL-17 deficiency increases diet-induced obesity and accelerates fatty tissue accumulation. While the effects of IL-12/23 blockade on these metabolic parameters are largely unknown in psoriasis patients, Phase 2 study of ustekinumab has shown a paradoxically increased serum levels IL-12 up to 13-fold in the first 12 weeks of treatment with a gradual decrease to above baseline levels at week 32., IL-12 is a pro-atherogenic cytokine that induces the production of serum triglyceride and Chol and causes higher insulin resistance.,,,, As opposed to our traditional understanding, this phenomenon suggests that anti-cytokine antibodies might produce agonists, rather than antagonist effect, especially in the induction period, which may explain findings of increased triglyceride level in this study., There are several limitations in this study. First, the study was a retrospective analysis of consecutive psoriasis patients under ustekinumab treatment. The results can only determine the association but not causation effect between metabolic parameters and the use of ustekinumab. Secondly, there is a possibility that other confounding factors such as diet and exercise habit that may affect the results.
| Conclusion|| |
This study illustrates the effect of IL-12/23 blockade by ustekinumab on metabolic parameters in patients with psoriasis. The present study denotes that despite clinical improvement after ustekinumab treatment, the coronary artery risk factors of BMI and triglyceride level can still increase. Furthermore, male patients are the only predicting factors to the elevation of triglyceride. These findings suggest that when treating patients with ustekinumab, physicians should still regularly follow-up patients' metabolic profiles. Moreover, these patients should be strongly counseled to control obesity to minimize cardiovascular risks associated with psoriasis during the treatment period.
Financial support and sponsorship
This study was supported by CMRPG 1F0061, 1F0062, MOST 104-2314-B-182A-082.
Conflicts of interest
Yu-Huei Huang has conducted clinical trials or received honoraria as a consultant for Abbvie, Celgene, Janssen-Cilag Pharmaceuticals, Novartis, Pfizer Pharmaceuticals. All other authors have no conflict of interest.
| References|| |
Azfar RS, Gelfand JM. Psoriasis and metabolic disease: Epidemiology and pathophysiology. Curr Opin Rheumatol 2008;20:416-22.
Takahashi H, Iizuka H. Psoriasis and metabolic syndrome. J Dermatol 2012;39:212-8.
Mallbris L, Akre O, Granath F, Yin L, Lindelöf B, Ekbom A, et al
. Increased risk for cardiovascular mortality in psoriasis inpatients but not in outpatients. Eur J Epidemiol 2004;19:225-30.
Gelfand JM, Troxel AB, Lewis JD, Kurd SK, Shin DB, Wang X, et al
. The risk of mortality in patients with psoriasis: Results from a population-based study. Arch Dermatol 2007;143:1493-9.
Abuabara K, Azfar RS, Shin DB, Neimann AL, Troxel AB, Gelfand JM. Cause-specific mortality in patients with severe psoriasis: A population study in the U.K. Br J Dermatol 2010;163:586-92.
Prey S, Paul C, Bronsard V, Puzenat E, Gourraud PA, Aractingi S, et al
. Cardiovascular risk factors in patients with plaque psoriasis: A systematic review of epidemiological studies. J Eur Acad Dermatol Venereol 2010;24 Suppl 2:23-30.
Myers WA, Gottliep AB, Maase P. Psoriasis and psoriatic arthritis: Clinical features and disease mechanism. Clin Dermatol 2006;24:438-47.
Fleming P, Kraft J, Gulliver WP, Lynde C. The relationship of obesity with the severity of psoriasis: A systematic review. J Cutan Med Surg 2015;19:450-6.
Eder L, Gladman DD. Atherosclerosis in psoriatic disease: Latest evidence and clinical implications. Ther Adv Musculoskelet Dis 2015;7:187-95.
Shlyankevich J, Mehta NN, Krueger JG, Strober B, Gudjonsson JE, Qureshi AA, et al
. Accumulating evidence for the association and shared pathogenic mechanisms between psoriasis and cardiovascular-related comorbidities. Am J Med 2014;127:1148-53.
Ahlehoff O, Skov L, Gislason G, Gniadecki R, Iversen L, Bryld LE, et al
. Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis: 5-year follow-up of a Danish nationwide cohort. J Eur Acad Dermatol Venereol 2015;29:1128-34.
Tam LS, Tomlinson B, Chu TT, Li TK, Li EK. Impact of TNF inhibition on insulin resistance and lipids levels in patients with rheumatoid arthritis. Clin Rheumatol 2007;26:1495-8.
Seriolo B, Paolino S, Sulli A, Fasciolo D, Cutolo M. Effects of anti-TNF-alpha treatment on lipid profile in patients with active rheumatoid arthritis. Ann N
Y Acad Sci 2006;1069:414-9.
Kiortsis DN, Mavridis AK, Filippatos TD, Vasakos S, Nikas SN, Drosos AA. Effects of infliximab treatment on lipoprotein profile in patients with rheumatoid arthritis and ankylosing spondylitis. J Rheumatol 2006;33:921-3.
Tzellos T, Kyrgidis A, Trigoni A, Zouboulis CC. Association of ustekinumab and briakinumab with major adverse cardiovascular events: An appraisal of meta-analyses and industry sponsored pooled analyses to date. Dermatoendocrinol 2012;4:320-3.
April WA, Cailtilin TH, Armstrong EJ. Psoriasis and metabolic syndrome: A systemic review and meta-analysis of observational studies. J Am Acad Dermatol 2013;68:654-62.
Ma C, Harskamp CT, Armstrong EJ, Armstrong AW. The association between psoriasis and dyslipidaemia: A systematic review. Br J Dermatol 2013;168:486-95.
Boehncke W, Boehncke S, Tobin AM, Kirby B. The 'psoriatic march': A concept of how severe psoriasis may drive cardiovascular comorbidity. Exp Dermatol 2011;20:303-7.
Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet 2007;370:263-71.
Tzellos T, Kyrgidis A, Zouboulis CC. Re-evaluation of the risk for major adverse cardiovascular events in patients treated with anti-IL-12/23 biological agents for chronic plaque psoriasis: A meta-analysis of randomized controlled trials. J Eur Acad Dermatol Venereol 2013;27:622-7.
Ryan C, Leonardi CL, Krueger JG, Kimball AB, Strober BE, Gordon KB, et al
. Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: A meta-analysis of randomized controlled trials. JAMA 2011;306:864-71.
Channual J, Wu JJ, Dann FJ. Effects of tumor necrosis factor-alpha blockade on metabolic syndrome components in psoriasis and psoriatic arthritis and additional lessons learned from rheumatoid arthritis. Dermatol Ther 2009;22:61-73.
Owczarczyk-Saczonek A, Placek W, Rybak-d'Obyrn J, Wygonowska E. Influence of ustekinumab on body weight of patients with psoriasis: An initial report. Postepy Dermatol Alergol 2014;31:29-31.
Voloshyna I, Mounessa J, Carsons SE, Reiss AB. Effect of inhibition of interleukin-12/23 by ustekinumab on the expression of leptin and leptin receptor in human THP-1 macrophages. Clin Exp Dermatol 2016;41:308-11.
Millán J, Pintó X, Muñoz A, Zúñiga M, Rubiés-Prat J, Pallardo LF, et al
. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention. Vasc Health Risk Manag 2009;5:757-65.
Cullen P. Evidence that triglycerides are an independent coronary heart disease risk factor. Am J Cardiol 2000;86:943-9.
Facchini FS, Hollenbeck CB, Jeppesen J, Chen YD, Reaven GM. Insulin resistance and cigarette smoking. Lancet 1992;339:1128-30.
Sentí M, Aubó C, Bosch M. The relationship between smoking and triglyceride-rich lipoproteins is modulated by genetic variation in the glycoprotein IIIa gene. Metabolism 1998;47:1040-1.
Amstrong AW, Harskamp CT, Dhillon JS, Armstrong EJ. Psoriasis and smoking: A systemic review and meta-analysis. Br J Dermatol 2014;170:301-14.
Aznaouridis K, Vlachopoulos C, Dima I, Ioakeimidis N, Stefanadis C. Triglyceride level is associated with wave reflections and arterial stiffness in apparently healthy middle-aged men. Heart 2007;93:613-4.
Julia S, Nehal NM, James GK, Strober B, Gudjonsson JE, Qureshi AA, et al
. Accumulating evidence for the association and shared pathogenic mechanisms between psoriasis and cardiovascular–related co-morbidities. Am J Med 2014;127:1148-53.
David W, Nima G, Mohamad N, Sangderk L, Judith B, Alan F, et al
. Role of host lipid metabolism and tissue macrophages in psoriasis. J Immunol 2011;186(1 Supplement):147.30.
Frank ON, Daniel HK, Jonathan B. Psoriasis. N
Engl J Med 2009;361:496-509.
Yoichiro I, Harumichi I. The IL-23/IL-17 axis in inflammation. J Clin Invest 2006;116:1218-22.
Baran A, Flisiak I, Jaroszewicz J, Świderska M. Effect of psoriasis activity on serum adiponectin and leptin levels. Postepy Dermatol Alergol 2015;32:101-6.
Cauza E, Cauza K, Hanusch-Enserer U, Etemad M, Dunky A, Kostner K, et al
. Intravenous anti TNF-α antibody therapy leads to elevated triglyceride and reduced HDL-cholesterol levels in patients with rheumatoid and psoriatic arthritis. Wien Klin Wochenschr 2002;114:1004-7.
Jung SH, Park HS, Kim KS, Choi WH, Ahn CW, Kim BT, et al
. Effect of weight loss on some serum cytokines in human obesity: Increase in IL-10 after weight loss. J Nutr Biochem 2008;19:371-5.
Blüher M, Fasshauer M, Tönjes A, Kratzsch J, Schön MR, Paschke R. Association of interleukin-6, C-reactive protein, interleukin-10 and adiponectin plasma concentrations with measures of obesity, insulin sensitivity and glucose metabolism. Exp Clin Endocrinol Diabetes 2005;113:534-7.
Dessi S, Batetta B, Spano O, Bagby GJ, Tessitore L, Costelli P, et al
. Perturbations of triglycerides but not of cholesterol metabolism are prevented by anti-tumour necrosis factor treatment in rats bearing an ascites hepatoma. Br J Cancer 1995;72:1138-43.
Carbo N, Costelli P, Tessitore L, Bagby GJ, López-Soriano FJ, Baccino FM, et al
. Anti-tumour necrosis factoralpha treatment interferes with changes in lipid metabolism in a tumour cachexia model. Clin Sci (Colch) 1994;87:249-55.
Esposito M, Mazzotta A, Saraceno R, Schipani C, Chimenti S. Influence and variation of the body mass index in patients treated with etanercept for plaque-type psoriasis. Int J Immunopathol Pharmacol 2009;22:219-25.
Zúñiga LA, Shen WJ, Joyce-Shaikh B, Pyatnova EA, Richards AG, Thom C, et al
. IL-17 regulates adipogenesis, glucose homeostasis, and obesity. J Immunol 2010;185:6947-59.
Mishra M, Kumar H, Bajpai S, Singh RK, Tripathi K. Level of serum IL-12 and its correlation with endothelial dysfunction, insulin resistance, proinflammatory cytokines and lipid profile in newly diagnosed type 2 diabetes. Diabetes Res Clin Pract 2011;94:255-61.
Nikołajuk A, Karczewska-Kupczewska M, Straczkowski M. Relationship between serum IL-12 and p40 subunit concentrations and lipid parameters in overweight and obese women. Metab Syndr Relat Disord 2015;13:336-42.
Uyemura K, Demer LL, Castle SC, Jullien D, Berliner JA, Gately MK, et al
. Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis. J Clin Invest 1996;97:2130-8.
Reddy M, Torres G, McCormick T, Marano C, Cooper K, Yeilding N, et al
. Positive treatment effects of ustekinumab in psoriasis: Analysis of lesional and systemic parameters. J Dermatol 2010;37:413-25.
Naldi L. Safety concerns of targeted therapies with special emphasis on treatment for plaque psoriasis. NTDV 2014;3:135-7.
[Table 1], [Table 2], [Table 3]