Table 2.

Immunoregulatory properties of garlic.

Immunoregulatory mechanism	Model/pathology involved	Garlic preparation (dose)	Immunoparameters evaluated	Conclusions	References
	3T3-L1 adipocytes stimulated with LPS/in vitro model of inflamed adipose tissue.	Cell incubation with alliin for 24 h (100 μmol/L).	Proinflammatory cytokines and adipocytokines IL-6, TNF-α, MCP-1, and adiponectin.	Alliin is capable of suppressing LPS inflammatory signals by generating an anti-inflammatory gene expression and prevented the increase in expression of proinflammatory cytokines IL-6 and MCP-1.	[30]
	Male Wistar rats/inflammation.	Gavage with garlic oil (10–200 mg/kg).	Cellularity of cervical lymph nodes. Production of Th1 cytokines IL-2 and IFN-γ and Th2-type cytokines IL-4 and IL-10.	Garlic oil enhances and shifts toward Th1-type response at low doses. It promotes an anti-inflammatory environment at high doses by shifting Th1-Th2 balance toward the Th2 type.	[21]
Modulating cytokine secretion	Preeclamptic placental explant tissue stimulated with LPS.	Garlic extract (10, 100, 500, and 1,000 μg/mL).	Cytokine levels of TNF-α, IL-6, IL-10, and sTRAIL.	Garlic at lower doses possesses an immunomodulatory effect on normal placenta by increasing production of IL-10 and in preeclamptic explants reduces production of inflammatory cytokines such as IL-6 and TNF-α. At higher doses, overall effect is one of cytokine synthesis inhibition and stimulation of sTRAIL production.	[31]
	Whole blood stimulated with LPS and human embryonic kidney cell line 293 (HEK293).	Garlic powder extracts (10 g/L), DADS (100 mol/L), and allicin (100 mol/L).	Cytokine levels of TNF-α, IL-1β, IL-10, and NF-κΒ activity.	Garlic compounds modulate inflammatory cytokines, leading to overall reduction of NF-κB activity.	[32]
	In vitro: peritoneal macrophage-mediated antitumoral activity.	Allicin (1, 10, and 100 ng/mL) for 20 h.	Cytotoxicity and phagocytosis assay. Nitrite and hydrogen peroxide production. Production of cytokines TNF-α, IL-1, and IL-6.	Allicin increases macrophage production of TNF-α and nitric oxide (NO) in a dose-dependent manner.	[33]
Phagocytosis and cell activation	Balb/c mice infected with Plasmodium yoelii/Malaria.	Allicin orally applied 3 or 9 mg/kg/day on days 0–2 (PI).	Pro- and anti-inflammatory cytokines IFN-γ, TNF-α, IL-12p70, IL-4, and IL-10.	Allicin reduced parasitemia and prolonged survival due to improved host immune responses. Enhancement of proinflammatory mediators IFN-γ, TNF-α, and IL-12p70. No changes in anti-inflammatory cytokines IL-4 and IL-10.	[34]
	In vitro assays: neutrophil-like cells (HL-60 cell line).	Garlic oil (1 μg/mL < 10 μg/mL) for 60 min.	Chemotactic responsiveness and motility of neutrophil-like cells.	Average migration speed of cells reduced after being treated with garlic oil, thereby resulting in anti-inflammatory activities through inhibition of assembly and disassembly of cytoskeleton inside the cell.	[22]
Activation of humoral immune response and synthesis of Ig	In vivo assays, white Leghorn chickens/viral and bacterial infection.	Dietary alliums: Allium sativum (G) and Allium cepa (O) (low doses: 10 g/kg (GL and OL) or high doses 30 g/kg (GH and OH)).	Antibodies, lymphocyte proliferation, and ratios of CD4+ : CD8+ and CD4− : CD8− lymphocytes.	GL and OL enhanced anti-NDV, anti-SRBC, and anti-BA antibody productions. Only GL- and GH had a comitogenic effect on splenocytes and thymocytes. Reduction in CD4+ and increase in CD4− : CD8− lymphocyte ratios were observed with GH or OH.	[35]
	Mouse mucosal.	OMG containing 1,500 mg/g of ajoene.	IgA production in feces or colon tissue.	Intestinal IgA level was increased by ajoene; thus, ajoene may have influenced B-cell stimulation or interleukin secretion.	[36]
Antiallergic response	In vitro assays: RBL-2H3 induced by (TNP) monoclonal antibody and the TNP (BSA-related) hapten carrier complex/allergic reactions. In vivo assays: Balb/c male mice i.v. administered anti-TNP IgE antibody and subsequent picryl chloride painting on the ear/allergic reactions.	AGE incubation (1.25, 2.5, and 5.0 g/100 g). AGE orally applied (10 mL/kg).	Histamine release by basophils. Ear swelling used as an index of immunoglobulin IgE-mediated skin reaction.	AGE significantly inhibited antigen- specific histamine release and decreased ear swelling. AGE may directly and/or indirectly modify functions of mast cells, basophils, and activated T lymphocytes, which play a leading role in allergic cascade reactions.	[37]
	Balb/c mouse allergic-airway inflammation/asthma.	3 IP injections of 14 kD fraction of AGE (20 mg/kg).	Percentages of lavage eosinophils. Mucus-producing goblet cells in airways. Perivascular and peribronchial inflammatory grades.	14 kD fraction of AGE is able to reduce allergic-airway inflammation hallmarks in murine model accompanied by increase in IFN-γ-level bronchoalveolar lavage.	[38]
Mitogenic stimulator	In vitro assays on immune cells/immunomodulation.	Garlic protein fractions: QR-1, QR-2, and QR-3.	Proliferation index in murine splenocytes/thymocytes and human PBL.	All three proteins exhibited mitogenic activity toward human PBL and murine splenocytes/thymocytes. Mitogenicity of QR-2 was the highest among the three immunomodulatory proteins.	[39]
	In vitro assays on PBMC and PMN incubated with or without 10 ng/mL of LPS.	Alliin (1 and 3.0 mg/mL).	Cytokine concentration: IL-1β, IL-6, TNF-α, and IL-2. Superoxide anion production. Phagocytosis.	Alliin induces PWM-cell proliferation, spontaneous production of IL-1β, as well as an increase in number of phagocyting cells and engulfed latex particles. Alliin causes decrease in mitogenic function of ConA.	[1]
Anti-inflammatory and antioxidant effects	Male albino rats (Rattus norvegicus)/gastric inflammation.	AGE orally (100–200 mg/kg).	Macroscopic appearance of gastric mucosa. Microbial count. Levels of TNF-α, SOD, CAT, and MPO enzyme activity.	Gastroprotective mechanism of AGE on gastric damage induced by Indomethacin through its anti-inflammatory actions and its antioxidant properties.	[28]

Aged garlic extract (AGE); malondialdehyde (MDA); myeloperoxidase (MPO); total glutathione (tGSH); superoxide dismutase (SOD); catalase (CAT); peripheral blood lymphocytes (PBL); peripheral blood mononuclear (PBMC); polymorphonuclear (PMN); pokeweed mitogen (PWM); tumor necrosis factor- (TNF-) related apoptosis-inducing ligand/Apo-2L (sTRAIL).