Table 2. Primary and secondary outcomes from individual studies.
| Source | LPS used | Primary outcome: cytokine secretion/production | Secondary outcome: toxicity of phthalates |
|---|---|---|---|
| Testicular macrophages, Sprague Dawly rats, DnBP (Zheng 2010 [63]) | No | ↑ IL-1 β | ND |
| Adherent splenocytes, Wistar rats, DEHP (Tonk 2012 [65]) | Yes, 15 μg/ml | ↑ TNF-α in adult group. ↔ TNF-α in juvenil group. | ND |
| Adherent splenocytes, Sprague Dawly rats, DEHP (Piebenbrink 2005 [62]) | Yes, 10 ng/ml (incubation ex-vivo for 24 hours) | ↔ TNF-α (5 weeks after exposure ended) | Still birth and early death of pups were low, results given in mean +/- SEM. Death in parental group not specified. Cell toxcicity ND. |
| Abdominal macrophages, Balb/c mice, BBzP (Hong 2004 [61]) | Yes, 1 og 10 ng/ml (incubation ex-vivo for 4 hours) | ↔ TNF-α | Unclear if assessed |
| Raw 264 cell line, BBzP (Hong 2004 [61]) | Yes, 10 ng/ml (incubation together with phthalates) | ↓ TNF-α | No data (crystal violet staining), conclusion is no cytoxcicity |
| THP-1 cell line, DEHP (Nishioka 2012 [71]) | No | ↑ TNF-α, IL-1 β and IL-8, ↔ IL-6 (mRNA expression: ↑ TNF-α, IL-1 β, IL-8 and IL-6) | ND |
| THP-1 cell line, DiNP (Bennasroune 2012 [69]) | Yes, 5ng/ml (cell viability) or 10 ng/ml (cytokine secretion) (administred 24h after phthalate exposure and incubation for another 24h) | ↑ TNF-α, ↔ IL-1 β and IL-8 | Cell viability, <10% decrease |
| THP-1 cell line, different monoesters (Glue 2002 [70]) | Yes, 1 μg/ml (only cytokine assessment)(incubation together with phthalates) | ↔ IL-1 β, IL-6, IL-12 α p35 (mRNA epxression) | Live cells per ml (tryphan blue), leathal phthalate monoester concentration when higher than 20 μg/ml. |
| Raw 264 cell line, MEHP (Kocbach 2012 [68]) | No | ↑ TNF-α | No data (PI/Hoechst staining, LDH), conclusion: no significant increase in toxcicity. |
| Peritoneal macrophages from transgenic mice, DnBP (Li 2013 [64]) | Yes, 100 ng/ml (only cytokine assessement) (incubation 6h after phthalates exposures) | ↓ TNF-α, IL-1 β and IL-6, ↔ IL-10 and IL-12 (both cytokine secretion and mRNA exression) | Data only in graph, mean +/- SD (tryphan blue), data as a representative flowcytometry sample with percentage of positiv cells (PIannexin V-staining). Conclusion: 5*10-5 M and 10-4 M significant cytotoxcity |
| Peritoneal macrophages from Balb/c mice, DEHP (Yamashita 2005 [67]) | No | ↑ TNF-±, IL-1 ±, IL-6 and IL-12 | ND |
| Peritoneal macrophages from Balb/c mice, DEHP (Yamashita 2002 [66) | Yes, 5 μg/ml (incubation 24 h after phthalate exposure) | Without LPS: ↑ TNF-± and IL-1 ±, With LPS: ↑ IL-1 ±, ↔ TNF-± | ND |
Footnote: BBzP: Butylbenzyl phthalate, DEHP: Di-2-ethylhexyl phthalate, DiNP: Di-iso-nonyl phthalate, DnBP: Di-n-butyl phthalate, IL: Interleukin, LDH: lactate dehydrogenase, MEHP: Mono-(2-ethylhexyl) phthalate, ND: not done, PI: Propidium Iodide, RAW 264 cell line: mouse leukemic monocyte-macrophage cell line, SD: standard deviation, SEM: standard error of the mean, THP-1 cell line: acute monocytic cell line, TNF: Tumour necrosis factor.