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Garlic is proposed to have immunomodulatory and anti-inflammatory properties. This paper shows that garlic powder extracts (GPE) and single garlic metabolites modulate lipopolysaccharide (LPS)-induced cytokine levels in human whole blood. GPE-altered cytokine levels in human blood sample supernatants reduced nuclear factor (NF)-[kappa]B activity in human cells exposed to these samples. Pretreatment with GPE (100 mg/L) reduced LPS-induced production of proinflammatory cytokines interleukin (IL)-1 [beta] from 15.7 [+ or -] 5.1 to 6.2 [+ or -] 1.2 [micro]g/L and tumor necrosis factor (TNF)-[alpha] from 8.8 [+ or -] 2.4 to 3.9 [+ or -] 0.8 [micro]g/L, respectively, whereas the expression of the anti-inflammatory cytokine IL-10 was unchanged. The garlic metabolite diallydisulfide (1-100 [micro]mol/L) also significantly reduced IL-1 [beta] and TNF-[alpha]. Interestingly, exposure of human embryonic kidney cell line (HEK293) cells to GPE-treated blood sample supernatants (10 or 100 mg/L) reduced NF-[kappa]B activity compared with cells exposed to untreated blood supernatants as measured by a NF-[kappa]B-driven luciferase reporter gene assay. Blood samples treated with extract obtained from unfertilized garlic (100 mg/L) reduced NF-[kappa]B activity by 25%, whereas blood samples treated with sulfur-fertilized garlic extracts (100 mg/L) lowered NF-[kappa]B activity by 41%. In summary, garlic may indeed promote an anti-inflammatory environment by cytokine modulation in human blood that leads to an overall inhibition of NF-[kappa]B activity in the surrounding tissue. KEY WORDS: * garlic * cytokines * nuclear factor-[kappa]B