Figure 1.

Inflammation, smoking, and monoamine metabolism. Nicotine increases the expression of tyrosine hydroxylase (TH) gene as depicted in green (+), thus decreasing tyrosine (Tyr) levels and increasing downstream catecholamine synthesis. Smoking also favors Type 2 helper cell (Th2) immunity over Type 1 helper cell (Th1) immunity, in turn, decreasing the activity, depicted in red (−), of indoleamine 2,3-dioxygenase (IDO), consequently maintaining tryptophan (Trp) levels and decreasing kynurenine (Kyn). Th2 immune activation favored by smoking also increases the activity of phenylalanine hydroxylase (PAH), depicted in green (+). Smoking inhibits monoamine oxidase enzyme, depicted in red (−) and decreases breakdown of serotonin (5-hydroxytryptamine, 5-HT) into 5-hydroxyindoleacetic acid (5-HIAA). Th1 immunity via interferon gamma (IFNγ) triggers reactive oxygen species (ROS)-induced depletion of tetrahydrobiopterin (BH4) leading to PAH dysfunction.