Three Cases of Previous Smokers with Rheumatoid Arthritis Who Did Not Respond to Tumor Necrosis Factor Inhibitors Were Treated Successfully with an Anti-Interleukin-6 Receptor Antibody

We report three cases of previous smokers who did not respond to TNF inhibitors but who responded successfully to an anti-interleukin-6 receptor antibody (tocilizumab (TCZ)). Case 1 is a 63-year-old woman whose smoking index was 200 and had been complaining of polyarthralgia since 1996. She started treatment with etanercept due to high disease activity, but her DAS28-CRP was 4.2. She was therefore switched to TCZ, which dramatically improved her symptoms; her DAS28-CRP had decreased to 2.1. Case 2 is a 64-year-old man whose smoking index was 1600 and had been complaining of polyarthralgia since 2006. Because his DAS28-CRP score increased over time to 5.9, etanercept and adalimumab were added sequentially, but he showed no response over the course of two years. The patient was therefore switched to TCZ, which dramatically improved his symptoms: his DAS28-CRP decreased to 2.7. Case 3 is a 48-year-old woman whose smoking index was 560 and had been complaining of pain in both knee joints since 2001. She was treated with adalimumab due to high disease activity but showed no response over the course of 1.5 years. The patient was therefore switched to TCZ, and her DAS28-CRP decreased to 1.8. An IL-6 blockade might be suitable for treating these 3 cases of previous smokers.

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Effect of soluble interleukin-6 receptor α and interleukin-6 secreted by polymorphonuclear leukocytes on tumor necrosis factor-α expression and its production by peripheral blood mononuclear cells

Mediators of Inflammation ◽

10.1080/09629350210000015746 ◽

2002 ◽

Vol 11 (5) ◽

pp. 325-328 ◽

Cited By ~ 2

Author(s):

E. Jablonska

Keyword(s):

Interleukin 6 ◽

Polymorphonuclear Leukocytes ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Tnf Α ◽

Interleukin 6 Receptor ◽

Factor Α ◽

Necrosis Factor

Background: It has recently been shown that soluble interleukin-6 receptor (sIL-6R) alone or complexed with interleukin (IL)-6, besides their regulatory role in a wide variety of both normal and abnormal biologic reactions mediated by IL-6, could be an effective stimulator of the cell function.Aims: The key question of the present study is whether the sIL-6Rα or sIL-6R with IL-6 released by polymorphonuclear leukocytes (PMN) can influence cytokine secretion such as tumor necrosis factor-α (TNF-α) by peripheral blood mononuclear cells (PBMC), which together with PMN develop the inflammatory and immune response of a host.Methods: Cells were isolated from heparinized whole blood of healthy persons. The PMN were cultured for 1 h at 37°C in 5% CO2. After incubation, the culture supernatant of PMN was removed and was added to PBMC. The PBMC were cultured for 1 h at 37°C in the same conditions. In the culture supernatants and lysates of PMN, we examined the concentrations of sIL-6R by enzyme-linked immunosorbent assay (ELISA). TNF-α was measured at both protein and mRNA levels. Protein levels were determined by ELISA. To examine TNF-α mRNA expression, we isolated mRNA from PBMC after culture, using TRIZOL Reagent. The quantity of mRNA TNF-α was determined by the Quantikine mRNA assay.Results and conclusion: The results obtained revealed that sIL-6R with IL-6 secreted by PMN may play a regulatory role in the immune response by modulating the TNF-α expression and its production by PBMC. This may have a significant influence on an early phase of the inflammation and other reactions mediated by TNF-α.

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Plasma profiles of IL-6 and TNF with fever-inducing doses of lipopolysaccharide in dogs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.259.1.r126 ◽

1990 ◽

Vol 259 (1) ◽

pp. R126-R132 ◽

Cited By ~ 6

Author(s):

D. R. LeMay ◽

L. G. LeMay ◽

M. J. Kluger ◽

L. G. D'Alecy

Keyword(s):

Statistical Analysis ◽

Tumor Necrosis Factor ◽

Interleukin 6 ◽

Tumor Necrosis ◽

Threshold Region ◽

Plasma Cytokine ◽

Changes Over Time ◽

Dose Dependent ◽

Necrosis Factor ◽

Over Time

This study was designed to test the tumor necrosis factor (TNF) WEHI 164 clone 13 bioassay and the interleukin 6 (IL-6) B9 bioassay for sensitivity to endogenously produced dog TNF and IL-6 and then to use these assays to examine the associations between these cytokines and lipopolysaccharide (LPS)-induced fever. When dogs were injected with LPS (40, 10, 1, 0.1, and 0.01 microgram/kg), the resulting fever was dose dependent. A plot of plasma cytokine changes over time following LPS injections showed that the plasma TNF-like activity appeared to increase in an all-or-none dose response, whereas the increase in plasma IL-6-like activity appeared to be log dose dependent. Plasma TNF-like and IL-6-like activity were then separately plotted against temperature change (fever). Statistical analysis supported the interpretation that both TNF-like and IL-6-like activity were related to LPS-fever in an all-or-none manner, with IL-6 having a threshold region. We conclude that if these cytokines are circulating mediators of fever, they may induce fever in an all-or-none fashion.

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Multilocus interactions at maternal tumor necrosis factor-α, tumor necrosis factor receptors, interleukin-6 and interleukin-6 receptor genes predict spontaneous preterm labor in European-American women

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2006.03.059 ◽

2006 ◽

Vol 194 (6) ◽

pp. 1616-1624 ◽

Cited By ~ 53

Author(s):

Ramkumar Menon ◽

Digna R. Velez ◽

Hyagriv Simhan ◽

Kelli Ryckman ◽

Lan Jiang ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Interleukin 6 ◽

Preterm Labor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

European American ◽

Tumor Necrosis Factor Receptors ◽

Interleukin 6 Receptor ◽

Factor Α ◽

Necrosis Factor

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Expression of interleukin-6 receptor (IL-6R) and gp130 mRNA in PC12 cells and sympathetic neurons: modulation by tumor necrosis factor α (TNF-α)

Brain Research ◽

10.1016/0006-8993(95)01210-9 ◽

1996 ◽

Vol 706 (1) ◽

pp. 71-79 ◽

Cited By ~ 42

Author(s):

P. März ◽

R.A. Gadient ◽

U. Otten

Keyword(s):

Tumor Necrosis Factor ◽

Pc12 Cells ◽

Interleukin 6 ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Sympathetic Neurons ◽

Tnf Α ◽

Interleukin 6 Receptor ◽

Factor Α ◽

Necrosis Factor

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Interleukin-6 receptor shedding is enhanced by interleukin-1? and tumor necrosis factor ? and is partially mediated by tumor necrosis factor ?-converting enzyme in osteoblast-like cells

Arthritis & Rheumatism ◽

10.1002/art.20727 ◽

2005 ◽

Vol 52 (1) ◽

pp. 84-93 ◽

Cited By ~ 28

Author(s):

Nathalie Franchimont ◽

C�cile Lambert ◽

Pascale Huynen ◽

Clio Ribbens ◽

Biserka Relic ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Interleukin 6 ◽

Tumor Necrosis ◽

Interleukin 1 ◽

Converting Enzyme ◽

Interleukin 6 Receptor ◽

Receptor Shedding ◽

Necrosis Factor

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Effects of Tocilizumab, an Anti-Interleukin-6 Receptor Antibody, on Serum Lipid and Adipokine Levels in Patients with Rheumatoid Arthritis

International Journal of Molecular Sciences ◽

10.3390/ijms20184633 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4633 ◽

Cited By ~ 10

Author(s):

Elinoar Hoffman ◽

Michal A. Rahat ◽

Joy Feld ◽

Muna Elias ◽

Itzhak Rosner ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Lipid Profile ◽

Interleukin 6 ◽

Density Lipoprotein ◽

High Sensitivity ◽

Mechanistic Explanation ◽

Receptor Antibody ◽

Increased Risk ◽

Interleukin 6 Receptor

Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease. Dyslipidemia is a known adverse effect of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody used in RA treatment. We aimed to assess the effect of TCZ on lipid profile and adipokine levels in RA patients. Height, weight, disease activity scores, lipid profile and atherogenic indices (AI), leptin, adiponectin, resistin, interleukin-6, and high-sensitivity C-reactive protein (CRP) were measured before and four months after initiation of TCZ in 40 RA patients and 40 healthy controls. Following TCZ treatment, total cholesterol, high density lipoprotein (HDL), and triglycerides were significantly elevated, but no significant changes in weight, body mass index (BMI), low density lipoprotein (LDL), and AI were observed. Compared with controls, significantly higher adiponectin levels were measured in the RA group at baseline. Following TCZ treatment, resistin levels and the leptin-to-adiponectin ratio increased, adiponectin levels decreased, and leptin levels remained unchanged. No correlation was found between the change in adipokine serum levels and changes in the disease activity indices, nor the lipid profile. In conclusion, the changes observed suggest a protective role for TCZ on the metabolic and cardiovascular burden associated with RA, but does not provide a mechanistic explanation for this phenomenon.

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