Access to the Spleen Microenvironment through Lymph Shows Local Cytokine Production, Increased Cell Flux, and Altered Signaling of Immune Cells during Lipopolysaccharide-Induced Acute Inflammation

Semaeva, Elvira; Tenstad, Olav; Skavland, Jørn; Enger, Marianne; Iversen, Per Ole; Gjertsen, Bjørn Tore; Wiig, Helge

doi:10.4049/jimmunol.0902049

Cited by 48 publications

(53 citation statements)

References 34 publications

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“…Postnodal lymph in normal rats has very low concentrations of IL-6, which is much lower than the concentration observed here. Rat lymph has similarly low concentrations of IL-1, IL-10 and TNF as we observed in human seroma fluid [14]. Olszewski et al measured several cytokines in lymph drained from the joints of rheumatoid arthritis patients and from control subjects [15].…”

Section: Discussionmentioning

confidence: 95%

Seroma Production After Breast Cancer Surgery has a Pro-Inflammatory Component

Szecsi¹

2012

TOBCANJ

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Seroma formation is the most prevalent postoperative sequela after breast cancer surgery. A total of 263 aspirations of seroma fluid in 42 patients were performed after mastectomy; cytokines were measured in 148 cases. The concentration of interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12p70 (IL-12) and tumor necrosis factor (TNF) were measured. The patients underwent 9.0 seroma aspirations on average (range 1-17) during an average of 30.7 days (range 7-72). The average cumulative seroma volume was 2056.1 mL (range 50-5130). In all samples, the maximal average concentrations of IL-6 (mean 10717 pg/mL, range 136-100000) and IL-8 (mean 7221 pg/mL, range 102-79828) were 55-200-fold above the serum/plasma levels of asymptomatic adults. In contrast, we observed levels similar to normal serum/plasma levels for IL-1 (mean 62.8 pg/mL, range 0-1226), IL-10 (mean 29.8 pg/mL, range 3.6-359), and lower-than-normal serum/plasma levels of TNF (mean 3.4 pg/mL, range 0-31.7) and IL-12 (mean 0.5 pg/mL, range 0-11.8). Patients with clinical infection had generally significant higher maximal IL-6 (p = 0.004) and IL-8 (0.019) than patients without clinical infection. However, most patients had no bacterial infection. None of the cytokines were associated with cumulative seroma volume, duration of seroma production or number of seroma aspirations. Seroma formation after mastectomy has a pro-inflammatory component, as indicated by the high levels of interleukin-6 and interleukin-8. However, these levels do not predict the course of seroma production.

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Section: Discussionmentioning

confidence: 95%

Seroma Production After Breast Cancer Surgery has a Pro-Inflammatory Component

Szecsi¹

2012

TOBCANJ

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“…The blood filtered through splenic capillaries goes out the spleen with the lymph. Very little is known about lymphatic flow through the spleen, but it appears important not only to maintain convective flow through splenic capillaries, but also because it represents a path for the efflux of activated lymphocytes and released cytokines from the spleen to the general circulation [24]. …”

Section: Spleen Microanatomy: the Pharmacologist Point Of Viewmentioning

confidence: 99%

Emerging Role of the Spleen in the Pharmacokinetics of Monoclonal Antibodies, Nanoparticles and Exosomes

Cataldi

Vigliotti

Mosca

et al. 2017

IJMS

197

151

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After being absorbed, drugs distribute in the body in part to reach target tissues, in part to be disposed in tissues where they do not exert clinically-relevant effects. Therapeutically-relevant effects are usually terminated by drug metabolism and/or elimination. The role that has been traditionally ascribed to the spleen in these fundamental pharmacokinetic processes was definitely marginal. However, due to its high blood flow and to the characteristics of its microcirculation, this organ would be expected to be significantly exposed to large, new generation drugs that can hardly penetrate in other tissues with tight endothelial barriers. In the present review, we examine the involvement of the spleen in the disposition of monoclonal antibodies, nanoparticles and exosomes and the possible implications for their therapeutic efficacy and toxicity. The data that we will review lead to the conclusion that a new role is emerging for the spleen in the pharmacokinetics of new generation drugs, hence suggesting that this small, neglected organ will certainly deserve stronger attention by pharmacologists in the future.

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“…Splenic lymphocytes predominantly regulate the pro-inflammatory conditions through cytokine production and modulation of immunocompetent cells (Semaeva et al 2010). The plant lectin Con A is a typical T-lymphocyte mitogen responsible for blastoid differentiation of T-lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of anti-inflammatory activity and standardisation of hydro-methanol extract of underground tuber ofDioscorea alata

Dey

Chowdhuri

Sarkar

et al. 2016

Pharmaceutical Biology

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Context The underground edible tuber of Dioscorea alata L. (Dioscoreaceae) is a functional food with high nutritive value and therapeutic potential. The tuber is known to possess antiinflammatory properties in traditional medicine. Objective The present study explores the anti-inflammatory activity and standardisation of D. alata tuber hydromethanol extract. Materials and methods Hydromethanol extract (70%) of D. alata tuber was chemically characterised using HPLC and GC-MS techniques. Murine lymphocytes were cultured for 48 h with six different concentrations (0-80 mg/mL) of the extract. The expression of nitric oxide (NO), TNF-a, COX-1, COX-2, and PGE 2 were evaluated using colorimetric and ELISA methods. Results Dioscorea alata extract inhibited the expression of NO and TNF-a with an IC 50 value of 134.51 ± 6.75 and 113.30 ± 7.44 mg/mL, respectively. The IC 50 values for inhibition of total COX, COX-1, COX-2 activities and PGE 2 level were 41.96 ± 3.07, 141.41 ± 8.99, 32.50 ± 1.69, and 186.34 ± 15.36 mg/mL, respectively. Inhibition of PGE 2 level and COX-2 activity was positively correlated (R 2 ¼ 0.9393). Gallic acid (GA), 4-hydroxy benzoic acid (4HBA), syringic acid (SYA), p-coumaric acid (PCA), and myricetin (MY) were identified and quantified using HPLC. GC-MS analysis revealed the presence of 13 different phytocompounds such as hexadecanoic acid, methyl stearate, cinnamyl cinnamate, and squalene. Conclusion The D. alata extract significantly down-regulated the pro-inflammatory signals in a gradual manner compared with control (0 mg/mL). Different bioactive phytocompounds individually possessing anti-inflammatory activities contributed to the overall bioactivity of the D. alata tuber extract. ARTICLE HISTORY

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Access to the Spleen Microenvironment through Lymph Shows Local Cytokine Production, Increased Cell Flux, and Altered Signaling of Immune Cells during Lipopolysaccharide-Induced Acute Inflammation

Abstract: Material

Cited by 48 publications

References 34 publications

Seroma Production After Breast Cancer Surgery has a Pro-Inflammatory Component

Seroma Production After Breast Cancer Surgery has a Pro-Inflammatory Component

Emerging Role of the Spleen in the Pharmacokinetics of Monoclonal Antibodies, Nanoparticles and Exosomes

Evaluation of anti-inflammatory activity and standardisation of hydro-methanol extract of underground tuber ofDioscorea alata

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