Table 2.
Immunological properties of major carotenoids against different diseases
| Carotenoids | In vitro/in vivo | Stimulus | Dose | Immunological effects | Ref. |
|---|---|---|---|---|---|
| Astaxanthin | Human | Phytohaemmaglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) | 2 and 8 mg | ↓ C‐reactive protein (CRP) at 2 mg; ↑Nkc activity and lymph proliferation at 8 mg; ↑IFN‐γ and IL‐6 at 8 mg; No change in IL‐2 and TNF‐α | Park et al., 2010 |
| Dog | Concanavalin A | 20 mg | ↑ lymph proliferation and NKc cytotoxicity; ↑ IgG, IgM; ↑ Beta cell population; no changes in the populations of CD4+, CD8+ and MHC class II | Chew et al., 2011 | |
| Cat | Con A, PHA, PWM | 10 mg | ↑ NKc cytotoxicity;↑cd5,cd4 population; ↓Beta cell population; no alteration in CD8 and MHCII; ↑IgG, IgM | Park et al., 2011 | |
| Human | –––––––––– | 4 mg | ↑ IgA secretion; no change in leukocyte count; reduction of pro‐oxidant‐antioxidant balance (PABC) | Baralic et al., 2015 | |
| Neutrophil from human peripheral blood | Lipopolysaccharide (LPS) | 5 μM | ↑ phagocytic (30%) and fungicide (28%) effects against Candida albicans; ↓ TNF‐α and IL‐6; ↑NO production | Macedo et al., 2010 | |
| U‐937 cell line | H2O2 | 10 μM | ↓TNF‐α, NF‐ĸB, IL‐6 and IL‐1β | Speranza et al., 2012 | |
| Astaxanthin stereoisomers | Mouse [K562 cell (target for NKc); lymphocytes and peritoneal macrophages] | –––––––– | 20 μmol·L−1 | ↑Lymph proliferation; ↑phagocytic activity; ↑NKc cytotoxicity; (3S, 3'S)‐trans‐astaxanthin was better than others | Sun et al., 2016 |
| Spleen and thymus from C57B/6 mice | PHA, ConA | 10−7‐10−9M | ↑ Ab production; ↑Thy‐1+ and Thy‐1− cell populations, No change in IL‐2 | Jyonouchi et al., 1991 | |
| Human PBMC (peripheral blood mononuclear cells) | PWM (for IgA); trinitrophenol‐modified keyhole limpet haemocyanin (TNP‐KLH); tetanus toxoid (for IgG) | 10−8mol·L−1 | ↑IgM; ↑IgG; ↑IgA | Jyonouchi et al., 1995 | |
| Peritoneal adherent cells of BALB/c mice | E.coli lipopolysaccharide (for Ab) | 2 × 10−7‐ 2 × 10−8M | ↑Thymocyte proliferation; ↑Ab production, ↑ TNF‐α and IL‐1α | Okai and Higashi‐Okai, 1996 | |
| Crocin | BV2 mouse microglial cells | LPS | 20 μM | ↓NO release in the cells stimulated with IFN‐γ and amyloid β (Aβ), ↓TNF‐α, NF‐ĸB, and IL‐1β | Nam et al., 2010 |
| Curcumin | Mice | E.G7/OT1 mouse lymphoma | 70 mg·kg−1·day−1 | ↑CD8 cytotoxicity , ↓ TGF‐β | Chang et al., 2012 |
| Mice | Mitogenic anti‐CD3/28 monoclonal antibodies (mAb) or antigenic stimulation by ovalbumin (OVA) | 1% of diet | ↓ NF‐ĸB activation; ↓ CD4 proliferation; ↓IL‐2 production (29.4%) in antigenic stimulation | Kim et al., 2009 | |
| Rat | Keyhole limpet haemocyanin (KLH) antigen | 40 mg·kg−1 | ↑IgG production | South et al., 1997 | |
| Curcumin + Cyclosporin‐A | Rat | PHA; ConA | 40 mg·kg−1·day−1 | ↑proliferation of lymph cells; No change in IFN‐γ and IL‐2 | Varalakshmi et al., 2008 |
| Curcumin | Human gastric epithelial cells (AGS) | H. pylori | 40 μM for IL‐8 80 μM for NF‐ĸB | ↓IKK activity, Suppression of IL‐8; no change in ERK1/2 and p38 | Foryst‐Ludwig et al., 2004 |
| Neutral unilamellar liposomes of curcumin | Mice | Sheep red blood cells (SRBC) | 200 μmol·Kg−1 | ↑Antibody titres; ↑phagocytic activity of macrophages; inhibition of delayed type hypersensitivity (DTH) reaction by about 39.75% | Antony et al., 1999 |
| Curcumin | Primary human CD4+ T cells | anti‐CD2/ CD3/CD28 antibody‐coated beads | 2 μg·mL−1 | ↓ T cell expansion; Down‐regulation of CD69 at early phase; up‐regulation of CCR7 and L‐selectin at late phase, ↓IL‐10, IL‐13, IL‐2, TNF‐α, and IFN‐γ | Kim et al., 2013 |
| RAW264.7 macrophages from mice | Lipopolysaccharide (LPS) | 5 μg·mL−1 | Down‐regulation of NF‐ĸB binding to the p40‐ĸB sequence; ↓kB binding activity; inhibition of IL‐12 secretion from macrophage | Kang et al., 1999a,b | |
| Splenic macrophages from mice | LPS; head‐killed Listeria monocytogenes (HKL) | 5 μg·mL−1 | Inhibition of IL‐12, ↑IL‐4; No change in IL‐10; ↓ IFN‐γ | Kang et al., 1999a,b | |
| Curcumin | DC from mice | LPS | 25 μM | Suppression of CD80,86, MHCII but not MHCI, ↓ TNF‐α, NF‐ĸB, IL‐6, and IL‐1β cytokines | Kim et al., 2005 |
| Human astrocyte cell line (U373‐MG) | LPS | 5 μM | ↓ IL‐6, ↓MMP‐9 enzyme activity, and MCP‐1 mRNA expression | Seyedzadeh et al., 2014 | |
| CD14+ monocytes, isolated from human peripheral blood | LPS; polycytidylic acid (polyI:C) | 30 μM | ↓DC‐induced CD4 proliferation; ↓dextran uptake by non‐stimulated cells; No significant increase in CD83,86; prevention of DC migration towards CCL19 and CCL21; ↓chemokines fractalkine (CX3CL1) and interferon producing factor (IP‐10), ↓ IL‐6 | Shirley et al., 2008 | |
| Human PBMCs; RAW253 | PHA (for IL‐2); IFN‐γ (for NKc); LPS | 0.01 and 0.05 μg·mL−1 | Inhibition of PHA‐induced T‐cell proliferation; ↑NK cell cytotoxicity; no significant decrease in TNF‐α, ↓IL‐2 and LPS‐induced NF‐ĸB; ↓NO product from macrophages | Yadav et al., 2005 | |
| Curcumin | RAW264.7 cells; Ba/F3 cells | LPS | 20 μM | ↓ NF‐ĸB, ↓Cox‐2 expression; inhibited dimerization of TLR4 in Ba/F3cells | Youn et al., 2006 |
| Curcumin and lutein | Chicks | LPS | 200 mg·kg−1 | Curcumin led to: ↑ beta cell proliferation (%5.6) and T cell proliferation (%30.4) as compared to lutein; | Rajput et al., 2013 |
| Lutein | Human (atherosclerosis patients) | ––––––––––– | 20 mg·day−1 | ↓monocyte chemoattractant protein‐1MCP‐1), ↓IL‐6 | Xu et al., 2013 |
| Silk lutein | Mice | LPS; ConA | 20 mg·kg−1 | ↑NKc activity; ↑Ab production; ↑CD3,CD4, lymph proliferation; ↑IFN‐γ and IL‐2 | Promphet et al., 2014 |
| FloraGloTM crystalline lutein | Cat | PHA,ConA,PWM | 10 mg·day−1 | ↑percentage of CD4,CD21 and IgG; no effect on CD8,MHCII; no change in IL‐2 | Kim et al., 2000a,b |
| FloraGloTM crystalline lutein | Dog | PHA,CnoA,PWM | 5‐20 mg | ↑CD4 (at 5 mg); ↑CD8,CD5,MHCII (at 20 mg), ↑IgG | Kim et al., 2000a,b |
| Lutein | Chickens | Salmonella LPS | 50 mg·kg−1 | ↓IL12, IL‐1β (in liver) ↑TLR‐4 mRNA (in spleen) | Moraes et al., 2016 |
| Lutein | Rat Muller cells (rMC‐1) | CoCl2 | 20 μM | ↓ COX‐2, No change in TNF‐α, ↓NF‐kB and IL‐1β | Li et al., 2012 |
| RAW264.7 and HaCaT | LPS, INF‐γ, TNF‐α (for COX‐2) | 30 μM | ↓COX‐2 mRNA; suppressed p38, JNK activation; ↓IL‐6 | Oh et al., 2013 | |
| SW‐1353 human | IL‐1β | 0.1 μmol·L−1 1 μmol·L−1 | ↑IL‐4; IL‐10, IL‐6 and TNF‐α not affected; ↑IFN‐γ (1 μmol L−1) and IL‐2 (0.1 μmol L−1); ↓NF‐kB (0.1 μmol L−1) | Di Filippo et al., 2012 | |
| Xanthophylls: lutein and zeaxanthin | Male finch | PHA | 7 μg·mL−1 | 21% difference in wing‐web‐swelling between carotenoid‐supplemented and control; Lutein and Zeaxanthin are different in cell‐mediated immune response by only 3% | McGraw and Ardia, 2004 |
| Meso‐zeaxanthin (MZ) | Balb/c mice | LPS | 25 μg·mL−1 | ↓iNOS and COX‐2 in macrophages; ↓TNF‐α, IL‐1β and IL‐6 | Firdous et al., 2015 |
| 40% of lutein and 60% of zeaxanthin | Hens/ chicks | LPS | 40 mg·kg−1 | ↓mRNA of IFN‐γ, IL‐6, IL‐1β; ↓LITAF; ↑IL‐10; IL‐4 not affected | Gao et al., 2012 |
| β‐carotene | Human | ––––––––––– | 60 mg·day−1 | ↑T cell CD4; ↑percentage of NK; ↑percentage of cells with markers for activation IL‐2 and transferrin | Watson et al., 1991 |
| Dog | ConA; PWM, PHA | 50 mg·day−1 | ↑IgG, not IgM; ↑CD4; CD8,CD21,MHC II not altered; No change in IL‐2 | Chew et al., 2000 | |
| Fish | A. hydrophila infection | 100 mg·kg−1 | ↑phagocytic activity | Anbazahan et al., 2014 | |
| Lutein, β‐carotene, astaxanthin | Spleen cells from mice (in vitro), In vivo | T‐dependent (TD) Antigen | 10–8 mol/1 | Lutein (↑Ab in vitro); all 3 carotenoids (↑Ab in vivo); astaxanthin (↑IgM more than others) | Jyonouchi et al., 1994 |
| β‐carotene | Cow | PHA, ConA, PWM | 300 mg for phagocyte; 600 mg for proliferation | ↑ Phagocyte effect of neutrophils; ↑lymph proliferation | Michal et al., 1994 |
| β‐carotene | Healthy women | PHA | 30 mg·day−1 | No effect on T lymphocyte proliferative response | Gossage et al., 2000 |
| Jejunum and ileum of mice after weaning | ––––––––––––––––– | 50 mg·kg−1 | ↑IgA concentrations in the jejunum; ↑IgA antibody‐secreting cells | Nishida et al., 2014 | |
| Aged humans | K562 (target for NKc) | 45 mg·day−1 | ↑34% NKc cytotoxicity; ↑31% total T cells | Wood et al., 2000 | |
| Mouse splenocytes; human peripheral blood lymphocytes | –––––––––––––––––– | 2.5, 5 μg·mL−1 | For human:↑ tumour cell lysis For murine Nkc: negative effect on NK cells; ↓lysis of YAC‐1 lymphoma cells | Ashfaq et al., 2000 | |
| RAW264 macrophage | LPS; INF‐γ | 10 μM | ↓IL‐12p40, IL‐6 and IL‐1β | Katsuura et al., 2009 | |
| β‐carotene | Peyer's patch (PP) cells were isolated from mice (ex vivo) | ConA | 5 mg·kg−1·day−1 | Weakly decreased the percentage of T cells; ↑IL‐2 | Yamaguchi et al., 2010 |
| Spleen and thymus from C57B/6 mice | PHA, ConA | 10–8 M | Ab and IL‐2 production didn't increase | Jyonouchi et al., 1991 | |
| PBMC | PWM (IgA); TNP‐KLH; tetanus toxoid (IgG) | 10–8 M | No increase in IgM and IgG; ↑IgA | Jyonouchi et al., 1995 | |
| Spleen,thymocytes from BALB/c mice | ConA; LPS (for Ab) | 2 × 10–8 to 2 × 10–7 M | ↑Thymocytes proliferation; ↑Ab production at 2 × 10‐7 M; ↑TNF‐α and IL‐1α | Okai and Higashi‐Okai, 1996 | |
| β‐carotene and Lycopene | Mice | –––––––––––––––––– | 300 mg·kg−1 | β‐carotene: ↑the percentages and total cell amounts of CD3+,CD4+,CD8+ Lycopene: ↑ the numbers of beta cells and T‐helper cells (CD4+ total cell numbers), ↑ IgG | Garcia et al., 2003 |
| PBMC from human | ConA | Tomato juice (330 mL·day−1): 40 mg lycopene and 1.5 mg β‐carotene | ↑IL‐2 and IL‐4 cytokines | Watzl et al., 1999 | |
| β‐cryptoxanthin | Rat | Myxomatosis vaccine | 5, 10 mg·kg−1 | ↑ CD4; No change in CD8; ↑IgM (all doses at 21 day); ↑IgG (10 mg at 14, 21 day; 5 mg at 21 day); ↑IL‐4 (5 mg at 21 day; 10 mg at 14, 21 day); No change in IFN‐γ | Ghodratizadeh et al., 2014 |
| RAW264 | LPS; IFN‐γ | 10 μM | mild suppression of IL‐12p40; ↓IL‐1β and IL‐6 | Katsuura et al., 2009 | |
| SW‐1353 human | IL‐1β | 1 μmol·L−1 | ↓IL‐10; IL‐4 not affected; inhibition of IL‐1α; ↓IFN‐γ, NF‐ĸB and IL‐2 | Di Filippo et al., 2012 | |
| Violaxanthin (isolated from C. ellipsoidea ) | Murine macrophage RAW 264.7 | LPS | 60 μM (below 100 μM) | ↓NO; ↓PGE2;↓INOS‐COX‐2 (mRNA); ↓binding to p65 DNA sequences (↓NF‐ĸB) | Soontornchaiboon et al., 2012 |
| Lycopene and lutein | Human | – | 500 mg full weight; (15 mg of carotenoid in corn oil) | Lycopene: ↑HLA‐DR, no change in other MHCII molecules. Lutein: no change | Hughes et al., 2000 |
| Carotenoid extract from Dunaliella salina algae (α‐carotene, β‐carotene, lutein and zeaxanthin) | Murine macrophage RAW264.7 | LPS | 5, 10, 25 μM | Inhibition of NO and PGE2; at 5 and 10 μM, the algae extract presented a significantly higher inhibitory activity for NO and IL‐1β than all‐trans‐β‐carotene; ↓IL‐1β , IL‐6, TNF‐α and NF‐kB | Yang et al., 2013 |
| Lycopene | Mice | Ovalbumin (OVA) | 4 mg 200·μL−1 of water | ↓ eosinophils; ↓IL‐4, IL‐5; IL‐13, and IFN‐γ not altered | Hazlewood et al., 2011 |
| Lycopene | Mice | The left anterior descending coronary artery (LAD) for post‐myocardial infarction (MI) model in mice | 10 mg·kg−1·day−1 | ↓TGF‐β1; ↓ caspase 3,8,9 (all in mRNA); ↓TNF‐α, NF‐kB and IL‐1β | He et al., 2015 |
| HUVECs | LPS | 20 μM | ↓CD14,TLR4, TNF‐α and NF‐ĸB | Bae and Bae, 2011 | |
| PBMC | K562 cell | 5 μM | ↑ NKc cytotoxicity and IFN‐γ | Li et al., 2014 | |
| PBMC | LPS; PHA | 4 μM | ↓IL‐10, IL‐2 and IFN‐γ; IL‐6, IL‐1ra not affected; ↑TNF‐α and IL‐1β | Bessler et al., 2008 | |
| Adipose tissue from mice; 3 T3‐L1 cells; human preadipocytes | TNF‐α | 2 μM | ↓MCP1in adipose tissue from mice and 3 T3‐L1; ↓IL‐1β, IL‐6 and NF‐ĸB (↓ phosphorylated IKKα/β in 3 T3‐L1) | Gouranton et al., 2011 | |
| Human THP‐1 macrophage | Cigarette smoke extract (CSE) | 2 μM | ↓NF‐ĸB; ↓IL‐8; ↓ROS production; ↓NOX‐4 expression | Simone et al., 2011 | |
| Lycopene | Pancreatic acinar cells from rat | Cerulein, a cholecystokinin (CCK) analogue | 5 μmol·l−1 | ↓ROS; IL‐6, NF‐kB activation | Kang et al., 2011 |
| RAW 264.7 macrophage | LPS | 0.5–2 μM | ↓JNK phosphorylation; no effect on p38 and ERK1/2 phosphorylation; ↓ TNF‐α (at 1 μM), IL‐1β (at 2 μM), NF‐kB (at 2 μM), and IL‐6 (at 0.5 μM) | Marcotorchino et al., 2012 | |
| PBMCs | Concanavalin A, anti‐CD3 (for T‐cell activation) | 1.18–2.93 μg·mL−1 | ↓T lymph proliferation; ↓CD69 in T‐cell subsets (at 1.18 μg·mL−1); ↓IL‐2 | Mills et al., 2012 | |
| RAW264.7 | Gliadin in association with IFN‐γ | 20 μM | ↓iNOS and NF‐kB; ↓signal transducer and activator of transcription‐1α (STAT‐1α); ↓COX‐2; ↓interferon regulatory factor‐1(IRF‐1) | De Stefano et al., 2007 | |
| PBMC | LPS; PMA (for INF‐γ, IL‐2) | 0.25 μM | ↓IL‐10; ↓IL‐1ra; no change in IL‐1β; ↓IL‐2, TNF‐α and IFN‐γ | Bergman et al., 2010 | |
| RAW 264.7 | LPS | 10 μM | ↓NO; ↓INOS (at both protein and mRNA levels); COX‐2 not affected | Rafi et al., 2007 |