Three studies examined smoking and nonsmoking subjects without periodontitis and found smokers had significantly higher synthesis of lipoxygenases and isoprostanes in the extracted periapical granuloma [83], higher whole salivary IL-1 beta and IL-6 (P < 0.05) [93] but a lower total amount of platelet-derived growth factor (PDGF-AB) (P = 0.014) in gingival crevicular fluid [85]. This evidence concerns the gene IL6 and periodontitis.