Profile of Urinary Cytokines in Kawasaki Disease: Non-Invasive Markers

This cohort study aimed to investigate urinary cytokines expression to help identify a less invasive method of cytokine detection for Kawasaki disease (KD). Patients with confirmed KD were recruited. Patients with fever or urinary tract infection (UTI) were enrolled as control groups. Urinary samples were collected before and 3 days after intravenous immunoglobulin (IVIG) treatment. The levels of cytokines were detected by MILLPLEX® MAP human multiplex assay. All cytokines, i.e., epidermal growth factor (EGF), interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-13, IL-17A, IL-33, interferon-gamma-induced protein (IP)-10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) except monocyte chemoattractant protein (MCP)-1 were significantly higher in the KD group, compared with the fever-control (FC) group, whereas the expressions of IFN-γ, IL-1β, IL-6, IL-8, IL-17A, IL-33, MCP-1, MIP-1β, and TNF-α were significantly lower in the urine of KD patients, as compared with the UTI group. The expressions of EGF, IFN-γ, IL-8, IL-13, and IL-17A were higher in the urine of KD patients than in the FC group, whereas the level of IL-1β was lower in KD than in the UTI group after age adjustment by logistic regression. Levels of IL-6, IL-8, IL-13, IP-10, and MCP-1 were significantly higher in the pre-IVIG urine of KD patients than in the post-IVIG treatment group. Additionally, urine IL-4 and blood C-reactive protein were higher in the KD group with coronary artery lesion (CAL) than in the non-CAL group. Results of this study provide a new view of urinary cytokine expression in the disease progress of KD, which may help clinicians to predict and prevent morbidity early and non-invasively.

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Increased Numbers of Circulating Th22 and Th17 Cells in Patients with Kawasaki Disease

10.21203/rs.3.rs-861832/v1 ◽

2021 ◽

Author(s):

Zhang Liwen ◽

Huang Zhiying ◽

Xue Mei ◽

Zhang Xiaoyu ◽

Wang Fei ◽

...

Keyword(s):

Kawasaki Disease ◽

Th17 Cells ◽

Direct Evidence ◽

Ivig Therapy ◽

Th1 Cells ◽

T Helper ◽

Reactive Protein ◽

Tnf Α ◽

Enzymelinked Immunosorbent Assay ◽

Ifn Γ

Abstract Background T-helper (Th) 22 and Th17 cells are involved in the pathogenesis of Kawasaki Disease (KD). Methods A total of 43 patients with freshly diagnosed KD and 20 age-/gender-matched healthy controls (HC) were examined for the numbers of Th22, Th17 and Th1 cells were quantified by flow cytometry. The concentrations of serum IL-22, IL-17, IFN-γ and TNF-α were examined by enzymelinked immunosorbent assay. Results In comparison with those in the HC, significantly increased numbers of Th22 and Th17 cells, but not Th1 cells, and increased levels of serum IL-22 and IL-17, but not IFN-γ, were detected in KD patients. Stratification analysis indicated the numbers of both Th22 and Th17 cells and the concentrations of serum IL-22 and IL-17 in KD patients with coronary artery lesions (CAL) were significantly greater than that in those with noncoronary artery lesions (NCAL). Treatment with the intravenous immunoglobulin (IVIG) therapy significantly decreased numbers of Th22 and Th17 cells and concentrations of serum IL-22 and IL-17 in KD patients. The concentrations of serum IL-22 and IL-17 were correlated positively with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values as well as N-terminal pro-brain natriuretic peptide (NT-proBNP) in those patients respectively. Conclusions Our study provided direct evidence that Th22 and Th17 cells might contribute to the pathogenesis of KD.

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Increased Numbers of Circulating Th22 and Th17 Cells in Children With Kawasaki Disease

10.21203/rs.3.rs-932685/v1 ◽

2021 ◽

Author(s):

Zhang Liwen ◽

Huang Zhiying ◽

Xue Mei ◽

Zhang Xiaoyu ◽

Wang Fei ◽

...

Keyword(s):

Kawasaki Disease ◽

Th17 Cells ◽

Ivig Therapy ◽

Th1 Cells ◽

Th22 Cells ◽

Reactive Protein ◽

Th 17 ◽

Tnf Α ◽

Ifn Γ ◽

Pathogenic Process

Abstract T-helper (Th) 17 and Th22 cells are critical for the pathogenic process of Kawasaki Disease (KD). A total of 43 children with freshly diagnosed KD and 20 healthy controls (HC) were quantified for the numbers of Th17, Th22 and Th1 cells by flow cytometry. The concentrations of serum IL-17, IL-22, IL-6, IFN-γ and TNF-α were examined by ELISA. Compared to those in the HC, significantly increased numbers of Th17 and Th22 cells, but not Th1 cells, and higher levels of serum IL-17 and IL-22, but not IFN-γ, were found in KD patients. Stratification analysis indicated the numbers of both Th17 and Th22 cells and the concentrations of serum IL-17 and IL-22 in KD patients with coronary artery lesions (CAL) were significantly greater than that in those with noncoronary artery lesions (NCAL). Treatment with the intravenous immunoglobulin (IVIG) therapy significantly decreased numbers of Th22 and Th17 cells as well as the serum concentrations of IL-22 and IL-17 in KD patients. The concentrations of serum IL-22 and IL-17 were correlated positively with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values as well as N-terminal pro-brain natriuretic peptide (NT-proBNP) in those patients respectively. Conclusion: Our study provided direct evidence that Th22 and Th17 cells might contribute to the pathogenesis of KD.

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Anlotinib Combined With Anti-PD-1 Antibodies Therapy in Patients With Advanced Refractory Solid Tumors: A Single-Center, Observational, Prospective Study

Frontiers in Oncology ◽

10.3389/fonc.2021.683502 ◽

2021 ◽

Vol 11 ◽

Author(s):

Min Yuan ◽

Zhongzheng Zhu ◽

Wei Mao ◽

Hui Wang ◽

Hong Qian ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Adverse Events ◽

Solid Tumors ◽

Immune Cell ◽

Vascular Endothelial ◽

Immune Cell Subsets ◽

Tnf Α ◽

Ifn Γ ◽

Endothelial Growth Factor

IntroductionAnlotinib (AL3818) is a novel multi-target tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR) and suppressing tumor growth. Modulation of tumor suppressive immune microenvironment via the inhibition of vascular endothelial growth factor may augment the activity of immune checkpoint inhibitors. Here we described the results of safety, and clinical efficacy of anlotinib combined with immunotherapy in patients with advanced solid tumors, the serum cytokine levels, and peripheral blood T lymphocyte populations were detected simultaneously.MethodsTwenty six cases with advanced late-stage cancers including lung, gallbladder, endometrial, gastric, pancreatic, penile cancers and melanoma were treated since January 2019. Patients received a combination of anlotinib (12mg) once daily on day 1 to day 14 (21 days as a course) plus anti-PD-1 antibodies every 3 weeks until progression or intolerable toxicity. Imaging was performed every 6 weeks for the first year of therapy. Blood samples were collected from patients prospectively. Serum interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and circulating immune cell subsets were measured at baseline and after two cycles of treatment via flow cytometry.ResultsThere were ten tumor types enrolled with lung, gallbladder, cholangiocarcinoma and soft tissue sarcoma being the most common. Most patients had received front line treatments for metastatic disease (80.8%). The objective response rate (ORR) was 23.1%, including one complete response (CR) (3.8%) and five partial responses (PR) (19.2%) and a disease control rate (DCR=CR+PR+SD) of 80.8% (21 of 26). The median PFS was 8.37 months (95% CI: 6.5-10.0 months). Three patients (11.5%) had grade 3 treatment-related adverse events. There were no grade 4 or 5 treatment-related adverse events. Grades 3 toxicities included hand-foot syndrome (n=2) and hypertension (n=1). Higher serum IL-2, IL-4, IL-10, TNF-α, IFN-γ levels and lower ratios of CD4/CD8 T cells were found in the responders compared with non-responders.ConclusionsThe preliminary data showed that the combination of anlotinib and anti-PD-1 antibodies demonstrated promising durable antitumor efficacy with acceptable toxicity in patients with various advance tumors, and promoted favorable changes in serum IL-2, IL-4, IL-10, TNF-α, IFN-γ levels and circulating immune cell subsets in clinical responders. It is worth to further validate the efficacy in a randomized prospective trial.

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Clearance of inflammatory cytokines in patients with septic acute kidney injury during renal replacement therapy using the EMiC2 filter (Clic-AKI study)

Critical Care ◽

10.1186/s13054-021-03476-x ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Nuttha Lumlertgul ◽

Anna Hall ◽

Luigi Camporota ◽

Siobhan Crichton ◽

Marlies Ostermann

Keyword(s):

Acute Kidney Injury ◽

Growth Factor ◽

Replacement Therapy ◽

Kidney Injury ◽

Final Analysis ◽

Adsorptive Capacity ◽

Clearance Rates ◽

Plasma Cytokine ◽

Tnf Α ◽

Ifn Γ

Abstract Background The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance. Methods This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations. Results Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period. Conclusion EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal. Trial registration: NCT03231748, registered on 27th July 2017.

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Proinflammatory cytokines TNF-α and IFN-γ alter laminin expression under an apoptosis-independent mechanism in human intestinal epithelial cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00535.2003 ◽

2004 ◽

Vol 287 (3) ◽

pp. G592-G598 ◽

Cited By ~ 34

Author(s):

Caroline Francoeur ◽

Fabrice Escaffit ◽

Pierre H. Vachon ◽

Jean-François Beaulieu

Keyword(s):

Growth Factor ◽

Epithelial Cells ◽

Proinflammatory Cytokines ◽

Intestinal Epithelial Cells ◽

Intestinal Epithelial ◽

Laminin 5 ◽

Cell Functions ◽

Tnf Α ◽

Independent Mechanism ◽

Ifn Γ

Laminins are basement membrane molecules that mediate cell functions such as adhesion, proliferation, migration, and differentiation. In the normal small intestine, laminin-5 and -10 are mainly expressed at the base of villus cells. However, in Crohn's disease (CD), a major redistribution of these laminins to the crypt region of the inflamed ileal mucosa has been observed, suggesting a possible relationship between laminin expression and cytokine and/or growth factor production, which is also altered in CD. The aim of this study was to test the hypothesis that proinflammatory cytokines can modulate laminin expression by intestinal epithelial cells. The effect of TNF-α, IFN-γ, IL-1β, IL-6, and transforming growth factor (TGF)-β was analyzed on the expression of laminins in the normal human intestinal epithelial crypt (HIEC) cell line. When treated with a single cytokine, HIEC cells secreted small amounts of laminin-5 and -10. Only TNF-α and TGF-β induced a slight increase in the secretion of these laminins. However, in combination, TNF-α and IFN-γ synergistically stimulated the secretion of both laminin-5 and -10 in HIEC cells. Transcript analyses suggested that the upregulation of the two laminins might depend on distinct mechanisms. Interestingly, the TNF-α and IFN-γ combination was also found to significantly promote apoptosis. However, the effect of cytokines on the secretion of laminins was maintained even after completely blocking apoptosis by inhibiting caspase activities. These results demonstrate that laminin production is specifically modulated by the proinflammatory cytokines TNF-α and IFN-γ in intestinal epithelial cells under an apoptosis-independent mechanism.

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Synovial Cytokines Significantly Correlate with Osteoarthritis-Related Knee Pain and Disability: Inflammatory Mediators of Potential Clinical Relevance

Journal of Clinical Medicine ◽

10.3390/jcm8091343 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1343 ◽

Cited By ~ 16

Author(s):

Timo A. Nees ◽

Nils Rosshirt ◽

Jiji A. Zhang ◽

Tobias Reiner ◽

Reza Sorbi ◽

...

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Knee Pain ◽

Inflammatory Mediators ◽

Clinical Relevance ◽

Knee Oa ◽

Broad Variety ◽

Ifn Γ ◽

And Function ◽

Endothelial Growth Factor

The aim of this study was to identify inflammatory mediators of potential clinical relevance in synovial fluid (SF) samples of patients with knee osteoarthritis (OA). Therefore, radiographic OA severity, knee pain and function of 34 OA patients undergoing unicompartmental (UC) and bicompartmental (BC) knee arthroplasty were assessed prior to surgery and SF samples were analyzed for a broad variety of inflammatory mediators, including interleukins (ILs), interferons (IFNs), C-X-C motif ligand chemokines (CXCLs), and growth factors (nerve growth factor; NGF, vascular endothelial growth factor; VEGF, and stem cell growth factor β; SCGF-β) using multiplex assay. Significant differences were observed between the SF levels of different inflammatory markers. When compared to UC OA, significantly higher concentrations of IL-7, IL-8, IL-10, IL-12, IL-13, IFN-γ, VEGF and CXCL1 were detected in BC OA. Correlation analyses revealed significant associations between OA severity and IL-6, IL-8, IFN-γ, SCGF-β, VEGF, CXCL1. Interestingly, increases in both anti- (IL-10, IL-13) and pro-inflammatory (IL-7, IL-12, IFN-γ) cytokines, as well as growth factors (SCGF-β, VEGF), correlated significantly with the level of knee pain. Poorer knee function was associated with higher IL-6, IL-10, IL-12, IL-13, IL-18, βNGF, SCGF-β, VEGF and CXCL9 levels. In conclusion, this study provides an extensive profile of synovial inflammatory mediators in knee OA and identifies cytokines of potential clinical relevance. In fact, five of the mediators examined (IL-10, IL-12, IL-13, SCGF-β, VEGF) significantly correlate with both knee pain and function.

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Evaluation of the Effects of Peritoneal Lavage with Rosmarinus officinalis Extract against the Prevention of Postsurgical-Induced Peritoneal Adhesion

Planta Medica ◽

10.1055/a-1118-3918 ◽

2020 ◽

Vol 86 (06) ◽

pp. 405-414 ◽

Cited By ~ 1

Author(s):

Yasamin Roohbakhsh ◽

Vafa Baradaran Rahimi ◽

Samaneh Silakhori ◽

Hamed Rajabi ◽

Pouria Rahmanian-Devin ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Vehicle Group ◽

Vascular Endothelial ◽

Abdominal Adhesions ◽

Peritoneal Adhesion ◽

Tnf Α ◽

Endothelial Growth Factor

AbstractPostoperative adhesions are regarded as the major complication following abdominal surgery. Rosmarinus officinalis has shown antioxidative and anti-inflammatory effects. Therefore, we aimed to assess the influence of 70% v/v hydro-ethanolic extract of the aerial parts of R. officinalis against postoperative abdominal adhesions in a rat model. Forty-eight male Wistar rats (190 ± 20 g) were divided into six groups of eight: group 1 = normal group, without any surgical procedures, group 2 = control group, group 3 = vehicle group, and groups 3, 4, and 5 = experimental groups receiving 2 mL of 4, 2, or 1% w/v R. officinalis treatment. Adhesion levels were macroscopically examined. Additionally, the levels of inflammatory cytokines (interleukin-6, interleukin-1β, and TNF-α), growth factors (transforming growth factor-β1, and vascular endothelial growth factor), oxidative (NO, nitric oxide and MDA, malondialdehyde), and antioxidative (GSH, glutathione) factors were evaluated. Our results revealed that the adhesion score, interleukin-6, interleukin-1β, TNF-α, transforming growth factor-β1, vascular endothelial growth factor, NO, and MDA levels were significantly increased in the vehicle group, while the GSH level was diminished. R. officinalis treatment notably ameliorated the adhesion score following postoperative abdominal adhesions compared with the vehicle group. Our results also revealed that R. officinalis markedly reduced inflammatory cytokines, oxidative factors, fibrosis, and angiogenesis biomarkers, whereas it increased the antioxidative factor. Therefore, R. officinalis may be a potential candidate for the management of postoperative peritoneal adhesion.

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The Augmented Productions of Neopterin and Cytokines from Macrophages/monocytes in vitro

Pteridines ◽

10.1515/pteridines.1996.7.3.72 ◽

1996 ◽

Vol 7 (3) ◽

pp. 72-76

Author(s):

Tadashi Lizuka ◽

Mitsuyo Sasaki ◽

Hitomi Kamisako ◽

Ko Oishi ◽

Shigeru Uemura ◽

...

Keyword(s):

Kawasaki Disease ◽

Interleukin 1 ◽

Poly I:C ◽

Recombinant Interferon ◽

Preliminary Examination ◽

Tnf Α ◽

Ifn Γ ◽

Factor Α ◽

Necrosis Factor

Summary In Kawasaki disease patients, increases in excretion of urinary neopterin coincided with fever and monocytosis in peripheral blood. We examined the products of neopterin, tumor necrosis factor-α (TNFα) and Interleukin-1 β (1L-1β) from healthy adult macrophages/monocytes (Mφ>/M), after stimulation with several activators to obtain some understanding of Kawasaki disease. Upon stimulation with either lipopolysaccharide (LPS) or polyinosinate-polycytidylate (Poly I:C), the Mφ/M released neopterin and pyogenic products (TNF-α or 1L-1β). The release of neopterin was eliminated by the addition of the anti-interferon-y antibody. The production of both TNF-α, 1L-1β and neopterin from Mφ/M upon stimulation of LPS was augmented in a co-culture with low dose recombinant interferon-y (rIFN-γ). Upon stimulation with rIFN-γ alone, however, the Mφ/M released neopterin but not the pyogenic products. A preliminary examination failed to detect. any difference in the response of the Mφ/M in adults annd children after stimulation with LPS. We concluded that some endotoxins could trigger the onset of Kawasaki disease and that endogenous IFN-γ can play an important role in the abnormality of Kawasaki disease patients

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Simultaneous Measurement of Antigen-Stimulated Interleukin-1β and Gamma Interferon Production Enhances Test Sensitivity for the Detection of Mycobacterium bovis Infection in Cattle

Clinical and Vaccine Immunology ◽

10.1128/cvi.00377-10 ◽

2010 ◽

Vol 17 (12) ◽

pp. 1946-1951 ◽

Cited By ~ 19

Author(s):

Gareth J. Jones ◽

Chris Pirson ◽

R. Glyn Hewinson ◽

H. Martin Vordermeier

Keyword(s):

Mycobacterium Bovis ◽

Gamma Interferon ◽

Interleukin 1Β ◽

Induced Responses ◽

Readout System ◽

Necrosis Factor Alpha ◽

Test Sensitivity ◽

Inflammatory Protein ◽

Tnf Α ◽

Ifn Γ

ABSTRACT In order to identify cytokines that may be useful as candidates for inclusion in diagnostic tests for Mycobacterium bovis infection in cattle, we compared the levels of gamma interferon (IFN-γ), interleukin 1β (IL-1β), IL-4, IL-10, IL-12, macrophage inflammatory protein 1β (MIP-1β), and tumor necrosis factor alpha (TNF-α) in whole-blood cultures from tuberculosis (TB) reactor animals or TB-free controls following stimulation with M. bovis-specific antigens (purified protein derivative from M. bovis [PPD-B] or ESAT-6/CFP-10). In addition to IFN-γ responses, the production of IL-1β and TNF-α was also statistically significantly elevated in TB reactor cattle over that in uninfected controls following stimulation with PPD-B or ESAT-6/CFP-10 peptides. Thus, we evaluated whether the use of these two additional readouts could disclose further animals not detected by measuring IFN-γ alone. To this end, receiver operating characteristic (ROC) analyses were performed to define diagnostic cutoffs for positivity for TNF-α and IL-1β. These results revealed that for ESAT-6/CFP-10-induced responses, the use of all three readouts (IFN-γ, TNF-α, and IL-1β) in parallel increased the sensitivity of detection of M. bovis-infected animals by 11% but also resulted in a specificity decrease of 14%. However, applying only IFN-γ and IL-1β in parallel resulted in a 5% increase in sensitivity without the corresponding loss of specificity. The results for PPD-B-induced responses were similar, although the loss of specificity was more pronounced, even when only IFN-γ and IL-1β were used as readout systems. In conclusion, we have demonstrated that the use of an additional readout system, such as IL-1β, can potentially complement IFN-γ by increasing overall test sensitivity for the detection of M. bovis infection in cattle.

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Circulating Vascular Endothelial Growth Factor, C-reactive Protein and Urinary Neopterin Concentrations During dose-dense Chemotherapy

Pteridines ◽

10.1515/pteridines.2008.19.1.65 ◽

2008 ◽

Vol 19 (1) ◽

pp. 65-71

Author(s):

Bohuslav Melichar ◽

Anna Balloková ◽

Eva Malirová ◽

Lubor Urbánek ◽

Lenka Krcmová ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Weekly Paclitaxel ◽

Vascular Endothelial ◽

C Reactive Protein ◽

Reactive Protein ◽

Urinary Neopterin ◽

Dose Dense ◽

Factor C ◽

Endothelial Growth Factor

Abstract Angiogenesis plays a crucial role in tumor progression. Prominent among angiogenic factors is vascular endothelial growth factor (VEGF). VEGF is produced by cancer cells as well as by the cells infiltrating tumor stroma, mainly macrophages. Macrophage activation may be assessed by measuring serum or urinary neopterin. Systemic inflammatory response could be evaluated by measuring serum C-reactive protein concentrations. The aim of the present study was to examine the effect of a regimen combining dose dense combination of doxorubicin and cyclophosphamide with sequential weekly paclitaxel on plasma VEGF, urinary neopterin and serum C-reactive protein concentrations. Thirty-four female patients with histologically verified breast carcinoma treated with dose-dense regimen combining doxorubicin and cyclophosphamide with sequential weekly paclitaxel administration were studied. Plasma VEGF was measured by enzyme-linked immunosorbent assay. Urinary neopterin was determined by high performance liquid chromatography. Compared to baseline plasma VEGF was significantly decreased one week after the start of therapy. VEGF concentrations subsequently increased, but this increase was significant compared to baseline only at week 16. Urinary neopterin was significantly increased compared to baseline at every visit with the exception of visits 12 and 20 at which the significance was borderline. Serum C-reactive protein was increased compared to baseline only at visits 4, 6 and 8. A positive correlation was observed between plasma VEGF and serum C-reactive protein at baseline and at visits 5 and 19. Significant correlations were observed between serum C-reactive protein and urinary neopterin at visits 6, 7, 9, 11, 14, 15 and 17. In conclusion, only minor changes in plasma VEGF and serum C-reactive protein were observed during dose-dense chemotherapy. In contrast, urinary neopterin was increased throughout the course of treatment. Correlations between VEGF and C-reactive protein and between Creactive protein and urinary neopterin were observed only at some time points.

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