Homoserine Lactones (HSLs) and Resorcinolic Lipids (RLs) originating from microbes and plants influence immune system, however, it is currently unclear whether HSLs and RLs are activators or suppressors of the cytokine network, especially in humans. A study has been carried out to investigate the effects of pure, synthetic HSLs and RLs with different chain lengths on pro-and anti-inflammatory cytokines produced by human blood monocyte cultures. Human monocytes (macrophages and lymphocytes) were collected from leukocyte-rich plasma, separated on a double density gradient, pre-treated with HSLs or Rls and then were inducted with standard either lipopolysaccharide or phytohemagglutinin stimulus. Quantitative assays for pro-and anti-inflammatory cytokines in the monocyte culture supernatants were performed using enzyme immunoassay kits for the quantitative determination of IL-1β, IL-2, IL-4, IL-10, TNF-α and IF-γ. We observed differences in cytokine production according to HSL and RL pre-treatment, increasing in the following order: IL-1β→IL-2≈IL-10≈TNF-α→IL-4→IF-γ. HSLs have been shown more pronounced inhibitory effects than Rls and long-chained homologs were more active than short-chained ones. Our study suggests that some small molecules originating from microbes and plants play an important role in cytokine network regulation and the immunomodulatory effect of HSLs and RLs may obstruct host defenses and affect inflammatory processes.