Immuno-Role of CCL28 Chemokine and Interleukin-29 in Methamphetamine Users with HSV-1 and Plaque-Induced Gingivitis

Abstract

Meth mouth is a term for the damage that methamphetamine can do to your teeth and gums. It can also make you more vulnerable to catch infections like herpes simplex virus type 1 (HSV-1). Plaque-induced gingivitis, alongside substance use and viral infection, may modify the levels of local immune mediators, such as CCL28 and interleukin-29 (IL-29). Different things are important for mucosal immunity and protecting against viral infections, although their amounts might change depending on the situation. The study aimed to investigate the immunological roles of CCL28 chemokine and IL-29 in methamphetamine users, both infected and uninfected with HSV-1, as well as in individuals with plaque-induced gingivitis. A case-control study was conducted from November 2024 to May 2025 involving 88 healthy male participants aged 20 to 35 years. The subjects were classified into four categories: healthy controls (n=25), methamphetamine users without HSV-1 (n=22), methamphetamine users with HSV-1 (n=21), and non-drug-using gingivitis patients without HSV-1 (n=20). PerioPaper strips were utilized to obtain samples of gingival crevicular fluid (GCF), which were subsequently analyzed for CCL28 and IL-29 concentrations using ELISA. Bleeding on probing (BOP%) and gingival crevicular fluid (GCF) volume were two clinical metrics. CCL28 levels peaked in healthy persons (420.90 ± 55.86 pg/mL) and decreased gradually in methamphetamine users (380.45 ± 24.80 pg/mL), meth + HSV-1 users (342.56 ± 10.84 pg/mL), and gingivitis patients (306.74 ± 10.34 pg/mL) (p<0.0001). IL-29 levels were lowest in healthy controls (205.75 ± 21.59 pg/mL) and highest in methamphetamine users (226.43 ± 4.84 pg/mL), co-infected persons (241.45 ± 4.75 pg/mL), and gingivitis patients (257.14 ± 4.53 pg/mL) (p<0.0001).CCL28 and IL-29 levels showed a strong negative correlation in all but the meth-only group. Reduced CCL28 and elevated IL-29 in methamphetamine users and gingivitis patients suggest compromised mucosal defense alongside heightened antiviral signaling. The use of amphetamine plus an HSV-1 infection seem to make these changes in the immune system worse, which could make gum disease worse.